INVOLUNTARY EFFECTORS The autonomic nervous system helps regulate the activities of cardiac muscle, smooth muscles, and glands. In this regulation, impulses are conducted from the CNS by an axon that synapses with a second autonomic neuron. It is the axon of this second neuron in the pathway that innervates the involuntary effectors. L E A R N I N G O U T C O M E S After studying this section, you should be able to: 1. Describe the organization of autonomic motor neurons. 2. Describe how neural regulation of smooth and cardiac muscles differs from neural regulation of skeletal muscles. Figure 9.1 The autonomic system has preganglionic and post-ganglionic neurons. The preganglionic neurons of the autonomic system have cell bodies in the CNS, whereas the postganglionic neurons have cell bodies within autonomic ganglia. The sympathetic and parasympathetic divisions differ in the particular locations of their preganglionic neuron cell bodies within the CNS, and in the location of their ganglia. CNS Autonomic motor nerves innervate organs whose functions are not usually under voluntary control. The effectors that respond to autonomic regulation include cardiac muscle (the heart), smooth muscles, and glands. These effectors are part of the visceral organs (organs within the body cavities) and of blood vessels. The involuntary effects of autonomic innervation contrast with the voluntary control of skeletal muscles by way of somatic motor neurons. Autonomic Neurons Neurons of the peripheral nervous system (PNS) that conduct impulses away from the central nervous system (CNS) are known as motor, or efferent, neurons (chapter 7, section 7.1) . There are two major categories of motor neurons: somatic and autonomic. Somatic motor neurons have their cell bodies within the CNS and send axons to skeletal muscles, which are usually under voluntary control. This was briefly described in chapter 8 (see fig. 8.28), in the section on the reflex arc. The control of skeletal muscles by somatic motor neurons is discussed in depth in chapter 12, section 12.5. Unlike somatic motor neurons, which conduct impulses along a single axon from the spinal cord to the neuromuscular junction, autonomic motor control involves two neurons in the efferent pathway ( fig. 9.1 and table 9.1 ). The first of these neurons has its cell body in the gray matter of the brain or spinal cord. The axon of this neuron does not directly innervate the effector organ but instead synapses with a second neuron within an autonomic ganglion (a ganglion is a collection of cell bodies outside the CNS). The first neuron is thus called a preganglionic neuron. The second neuron in this pathway, called a postganglionic neuron, has an axon that extends from the autonomic ganglion to an effector organ, where it synapses with its target tissue ( fig. 9.1 ). Preganglionic autonomic fibers originate in the midbrain and hindbrain and in the upper thoracic to the fourth sacral levels of the spinal cord. Autonomic ganglia are located in the head, neck, and abdomen; chains of autonomic ganglia also parallel the right and left sides of the spinal cord. The origin of the preganglionic fibers and the location of the autonomic ganglia help to distinguish the sympathetic and parasympathetic divisions of the autonomic system, discussed in later sections of this chapter. Autonomic ganglion Involuntary effector Smooth muscle Preganglionic neuron Postganglionic neuron 244 The Autonomic Nervous System 245 Table 9.1 | Comparison of the Somatic Motor System and the Autonomic Motor System FeatureSomatic MotorAutonomic Motor Effector organs Skeletal muscles Cardiac muscle, smooth muscle, and glands Presence of ganglia No ganglia Cell bodies of postganglionic autonomic fibers located in paravertebral, prevertebral (collateral), and terminal ganglia Number of neurons from CNS to effector One Two Type of neuromuscular junction Specialized motor end plate No specialization of postsynaptic membrane; all areas of smooth muscle cells contain receptor proteins for neurotransmitters Effect of nerve impulse on muscle Excitatory only Either excitatory or inhibitory Type of nerve fibers Fast-conducting, thick (9–13 m m), and myelinated Slow-conducting; preganglionic fibers lightly myelinated but thin (3 m m); postganglionic fibers unmyelinated and very thin (about 1.0 m m) Effect of denervation Flaccid paralysis and atrophy Muscle tone and function persist; target cells show denervation hypersensitivity The sensory neurons that conduct information from the viscera for autonomic nerve reflexes can have the same anatomy as those sensory neurons involved in somatic motor reflexes (chapter 8, fig. 8.28). That is, the sensory information enters the spinal cord on the dorsal roots of the spinal nerves. However, some important visceral sensory information can instead enter the brain in cranial nerves. For example, information about blood pressure, plasma pH, and oxygen concentration is carried into the brain by sensory axons in cranial nerves IX and X. These are mixed nerves, containing both sensory and parasympathetic motor axons. Visceral Effector Organs Because the autonomic nervous system helps regulate the activities of glands, smooth muscles, and cardiac muscle, autonomic control is an integral aspect of the physiology of most of the body systems. Autonomic regulation, then, plays roles in endocrine regulation (chapter 11), smooth muscle function (chapter 12), the functions of the heart and circulation (chapters 13 and 14), and, in fact, all the remaining systems to be discussed. Although the functions of the target organs of autonomic innervation are described in subsequent chapters, at this point we will consider some of the common features of autonomic regulation. Unlike skeletal muscles, which enter a state of flaccid paralysis and atrophy when their motor nerves are severed, the involuntary effectors are somewhat independent of their innervation. Smooth muscles maintain a resting tone (tension) in the absence of nerve stimulation, for example. In fact, damage to an autonomic nerve makes its target tissue more sensitive than normal to stimulating agents. This phenomenon is called denervation hypersensitivity. Such compensatory changes can explain why, for example, the ability of the stomach mucosa to secrete acid may be restored after its neural supply from the vagus nerve has been severed. (This procedure is called vagotomy, and is sometimes performed as a treatment for ulcers.) In addition to their intrinsic (“built-in”) muscle tone, cardiac muscle and many smooth muscles take their autonomy a step further. These muscles can contract rhythmically, even in the absence of nerve stimulation, in response to electrical waves of depolarization initiated by the muscles themselves. Autonomic innervation simply increases or decreases this intrinsic activity. Autonomic nerves also maintain a resting tone, in the sense that they maintain a baseline firing rate that can be either increased or decreased. A decrease in the excitatory input to the heart, for example, will slow its rate of beat. The release of acetylcholine (ACh) from somatic motor neurons always stimulates the effector organ (skeletal muscles). By contrast, some autonomic nerves release transmitters that inhibit the activity of their effectors. An increase in the activity of the vagus, a nerve that supplies inhibitory fibers to the heart, for example, will slow the heart rate, whereas a decrease in this inhibitory input will increase the heart rate. | CHECKPOINT 1. Describe the preganglionic and postganglionic neurons in the autonomic system. Use a diagram to illustrate the difference in efferent outflow between somatic and autonomic nerves. 2. Compare the control of cardiac muscle and smooth muscles with that of skeletal muscles. How is each type of muscle tissue affected by cutting its innervation Explain it for oral

9.2 DIVISIONS OF THE AUTONOMIC NERVOUS SYSTEM Preganglionic neurons of the sympathetic division originate in the thoracic and lumbar levels of the spinal cord and send axons to sympathetic ganglia, which parallel the spinal cord. Preganglionic neurons of the parasympathetic division originate in the brain and in the sacral level of the spinal cord, and send axons to ganglia located in or near the effector organs. L E A R N I N G O U T C O M E S After studying this section, you should be able to: 3. Describe the structure of the sympathetic nervous system, locating the ganglia and the preganglionic and postganglionic neurons. 4. Explain the relationship between the sympathetic nervous system and the adrenal medulla. 5. Describe the structure and innervation pathways of the parasympathetic division of the autonomic system. The sympathetic and parasympathetic divisions of the autonomic system have some structural features in common. Both consist of preganglionic neurons that originate in the CNS and postganglionic neurons that originate outside of the CNS in ganglia. However, the specific origin of the preganglionic fibers and the location of the ganglia differ in the two divisions of the autonomic system. Sympathetic Division The sympathetic division is also called the thoracolumbar division of the autonomic system because its preganglionic fibers exit the spinal cord, in the ventral roots of spinal nerves, from the first thoracic (T1) to the second lumbar (L2) levels. Most sympathetic nerve fibers separate from the somatic motor fibers and synapse with postganglionic neurons within a double row of sympathetic ganglia, called paravertebral ganglia, located on either side of the spinal cord ( fig.  9.2 ). Ganglia within each row are interconnected, forming a sympathetic chain of ganglia that parallels the spinal cord on each lateral side. The myelinated preganglionic sympathetic axons exit the spinal cord in the ventral roots of spinal nerves, but they soon diverge from the spinal nerves within short pathways called white rami communicantes. The axons within each ramus enter the sympathetic chain of ganglia, where they can travel to ganglia at different levels and synapse with postganglionic sympathetic neurons. The axons of the postganglionic sympathetic neurons are unmyelinated and form the gray rami communicantes as they return to the spinal nerves and travel as part of the spinal nerves to their effector organs ( fig. 9.3 ). Because sympathetic axons form a component of spinal nerves, they are widely distributed to the skeletal muscles and skin of the body where they innervate blood vessels and other involuntary effectors. Divergence occurs within the sympathetic chain of ganglia as preganglionic fibers branch to synapse with numerous postganglionic neurons located in ganglia at different levels in the chain. Convergence also occurs here when a postganglionic neuron receives synaptic input from a large number of preganglionic fibers. The divergence of impulses from the spinal cord Spinal cord Posterior (dorsal) root Anterior (ventral) root Rami communicantes Spinal nerve Rib Sympathetic chain of paravertebral ganglia Sympathetic ganglion Vertebral body Figure 9.2 The sympathetic chain of paravertebral ganglia. This diagram shows the anatomical relationship between the sympathetic ganglia and the vertebral column and spinal cord. The Autonomic Nervous System 247 1. Preganglionic axons synapse with postganglionic neurons Dorsal root Dorsal root ganglion Spinal nerve Visceral effectors: Smooth muscle of blood vessels, arrector pili muscles, and sweat glands Sympathetic chain ganglion Sympathetic chain 2. Postganglionic axons innervate target organs White ramus Ventral root Splanchnic nerve Gray ramus Visceral effector: intestine Collateral ganglion (celiac ganglion) Spinal cord Preganglionic neuron Postganglionic neuron Figure 9.3 The pathway of sympathetic neurons. The preganglionic neurons enter the sympathetic chain of ganglia on the white ramus (one of the two rami communicantes). Some synapse there, and the postganglionic axon leaves on the gray ramus to rejoin a spinal nerve. Others pass through the ganglia without synapsing. These ultimately synapse in a collateral ganglion, such as the celiac ganglion. to the ganglia and the convergence of impulses within the ganglia can result in the mass activation of almost all of the postganglionic sympathetic neurons. This mass activation allows the entire sympathetic division to be tonically (constantly) active to a certain degree and to increase its activity in response to “fight-or-flight” situations (section 9.3). However, mass activation does not always occur. In response to particular visceral stimuli (such as changes in blood pressure, blood volume, and plasma osmolality), the CNS can direct appropriate increases or decreases in the activity of postganglionic sympathetic axons to the heart and kidneys that allows these organs to compensate for the changes and maintain homeostasis. Collateral Ganglia Many preganglionic fibers that exit the spinal cord below the level of the diaphragm pass through the sympathetic chain of ganglia without synapsing. Beyond the sympathetic chain, these preganglionic fibers form splanchnic nerves. Preganglionic fibers in the splanchnic nerves synapse in collateral, or prevertebral, ganglia. These include the celiac, superior mesenteric, and inferior mesenteric ganglia ( fig. 9.4 ). Postganglionic fibers that arise from the collateral ganglia innervate organs of the digestive, urinary, and reproductive systems. Adrenal Glands The paired adrenal glands are located above each kidney ( fig. 9.4 ). Each adrenal is composed of two parts: an outer cortex and an inner medulla. These two parts are really two functionally different glands with different embryonic origins, different hormones, and different regulatory mechanisms. The adrenal cortex secretes steroid hormones; the adrenal medulla secretes the hormone epinephrine (adrenaline) and, to a lesser degree, norepinephrine, when it is stimulated by the sympathetic system. The adrenal medulla can be likened to a modified sympathetic ganglion; its cells are derived from the same embryonic tissue (the neural crest, chapter 8) that forms postganglionic sympathetic neurons. Like a sympathetic ganglion, the cells of the adrenal medulla are innervated by preganglionic sympathetic fibers ( fig.  9.5 ). The adrenal medulla secretes epinephrine into the blood in response to this neural stimulation. The effects of epinephrine are complementary to those of the neurotransmitter norepinephrine, which is released from postganglionic sympathetic nerve endings. For this reason, and because the adrenal medulla is stimulated as part of the mass activation of the sympathetic system, the two are Explain

9.3 FUNCTIONS OF THE AUTONOMIC NERVOUS SYSTEM The sympathetic division of the autonomic system activates the body to “fight or flight,” largely through the release of norepinephrine from postganglionic neurons and the secretion of epinephrine from the adrenal medulla. The parasympathetic division often produces antagonistic effects through the release of acetylcholine from its postganglionic neurons. L E A R N I N G O U T C O M E S After studying this section, you should be able to: 6. Identify the neurotransmitters of the sympathetic and parasympathetic divisions, and the hormone released by the adrenal medulla. 7. Describe the effects of adrenergic stimulation on different organs, and identify the types of adrenergic receptors involved. 8. Describe the effects of parasympathetic nerve regulation, and explain how atropine and related drugs affect this regulation. 9. Describe and give examples of antagonistic, cooperative, and complementary actions of the sympathetic and parasympathetic divisions of the autonomic system. The sympathetic and parasympathetic divisions of the autonomic system affect the visceral organs in different ways. Mass activation of the sympathetic system prepares the body for intense physical activity in emergencies; the heart rate increases, blood glucose rises, and blood is diverted to the skeletal muscles (away from the visceral organs and skin). The theme of the sympathetic system has been aptly summarized in a phrase: “fight or flight.” The fight-or-flight concept can give the erroneous impression that the sympathetic division is activated only in emergencies. But unlike somatic motor neurons, sympathetic neurons display tonic (continuous) activity. As a result, sympathetic nerves tonically regulate the heart, blood vessels, and other organs. Also, whereas the fight-or-flight reaction stimulates the mass activation of sympathetic nerve activity, there is also a more tailored, moment-to-moment regulation of the cardiovascular system and kidneys by the sympathetic division. Unlike the fight-or-flight theme of the sympathetic division, there is no universally recognized phrase to describe the actions of the parasympathetic division. However, because many of its actions are opposite to those of the sympathetic division, the theme of the parasympathetic division might be described as rest and digest, or repast and repose. The effects of parasympathetic nerve stimulation are in many ways opposite to those produced by sympathetic stimulation. The parasympathetic system, however, is not normally activated as a whole. Stimulation of separate parasympathetic nerves can result in slowing of the heart, dilation of visceral blood vessels, and increased activity of the digestive tract. Visceral organs respond differently to sympathetic and parasympathetic nerve activity because the postganglionic axons of these two divisions release different neurotransmitters. CLIN ICAL APP LICATI O N Sympathomimetic drugs are those that mimic the effects of sympathoadrenal stimulation. Such drugs include the naturally occurring catecholamines (epinephrine, norepinephrine, and dopamine) and their analogs, as well as drugs that promote the release of epinephrine and norepinephrine, block their reuptake from the synaptic cleft, and block their degradation (such as the MAO inhibitor drugs discussed in chapter 7). Many of these drugs have medical uses, but some abused drugs are sympathomimetics. Amphetamine and its derivatives (methamphetamine and mephedrone) promote the presynaptic release of norepinephrine; cocaine blocks its reuptake into presynaptic terminals. Sympathomimetic toxicity can cause tachycardia, diaphoresis (profuse perspiration), and hypertension, and is frequently a cause of cardiac arrest and death from abused drugs.

Adrenergic and Cholinergic Synaptic Transmission Acetylcholine (ACh) is the neurotransmitter of all preganglionic axons (both sympathetic and parasympathetic). Acetylcholine is also the transmitter released by most parasympathetic postganglionic axons at their synapses with effector cells ( fig. 9.7 ). Transmission at these synapses is thus said to be cholinergic. The neurotransmitter released by most postganglionic sympathetic nerve fibers is norepinephrine (noradrenaline). Transmission at these synapses is thus said to be adrenergic. There are a few exceptions, however. Some sympathetic fibers that innervate blood vessels in skeletal muscles, as well as sympathetic fibers to sweat glands, release ACh (are cholinergic). 252 Chapter 9 Cranial parasympathetic nerves Terminal ganglion ACh ACh Visceral effectors Paravertebral ganglion ACh Adrenal medulla NE Visceral effectors Sympathetic (thoracolumbar) nerves ACh E, NE (hormones) Circulation Sacral parasympathetic nerves ACh Collateral ganglion NE Visceral effectors ACh ACh Visceral effector organs Figure 9.7 Neurotransmitters of the autonomic motor system. ACh  5  acetylcholine; NE  5  norepinephrine; E  5  epinephrine. Those nerves that release ACh are called cholinergic; those nerves that release NE are called adrenergic. The adrenal medulla secretes both epinephrine (85%) and norepinephrine (15%) as hormones into the blood. Since the cells of the adrenal medulla are embryologically related to postganglionic sympathetic neurons, it is not surprising that their hormones are epinephrine (about 85%) and norepinephrine (about 15%). Epinephrine differs from norepinephrine only in that the former has an additional methyl (CH 3 ) group, as shown in figure  9.8 . Epinephrine, norepinephrine, and dopamine (a transmitter within the CNS) are all derived from the amino acid tyrosine and are collectively termed catecholamines ( fig. 9.8 ). Where the axons of postganglionic autonomic neurons enter into their target organs, they have numerous swellings, called varicosities, that contain the neurotransmitter molecules. Neurotransmitters can thereby be released along a length of axon, rather than just at the axon terminal. Thus, autonomic neurons are said to form synapses en passant (“synapses in passing”) with their target cells ( fig.  9.9 ). Sympathetic and parasympathetic axons often innervate the same target cells, where they release different neurotransmitters that promote different (and usually antagonistic) effects.

Create a comparison poster of adrenergic vs. cholinergic receptors and effects

Responses to Adrenergic Stimulation Adrenergic stimulation—by epinephrine in the blood and by norepinephrine released from sympathetic nerve endings— has both excitatory and inhibitory effects. The heart, dilatory muscles of the iris, and the smooth muscles of many blood vessels are stimulated to contract. The smooth muscles of the bronchioles and of some blood vessels, however, are inhibited from contracting; adrenergic chemicals, therefore, cause these structures to dilate. The Autonomic Nervous System 253 H H Tyrosine (an amino acid) HO C C NH2 H COOH Sympathetic neuron Varicosity Smooth muscle cell HO DOPA (dihydroxyphenylalanine) HO H H C C NH2 H COOH (a) HO Dopamine (a neurotransmitter) HO H C H H C NH2 H Synaptic vesicle with norepinephrine (NE) Synapses en passant Parasympathetic neuron Axon of Sympathetic Neuron HO Norepinephrine (a neurotransmitter and hormone) HO H C OH H C NH2 NE H Adrenergic receptors OH Epinephrine (major hormone of adrenal medulla) HO H C OH H H C N H CH3 Figure 9.8 The catecholamine family of molecules. Catecholamines are derived from the amino acid tyrosine, and include both neurotransmitters (dopamine and norepinephrine) and a hormone (epinephrine). Notice that epinephrine has an additional methyl (CH 3 ) group compared to norepinephrine. Antagonistic effects Smooth muscle cell Cholinergic receptors ACh Because excitatory and inhibitory effects can be produced in different tissues by the same neurotransmitter, the responses must depend on the characteristics of the effector cells. To some degree, this is due to the presence of different membrane receptor proteins for the catecholamine neurotransmitters. (The interaction of neurotransmitters and receptor proteins in the postsynaptic membrane was described in chapter 7.) The two major classes of these receptor proteins are designated alpha- ( a ) and beta- ( b ) adrenergic receptors. Experiments have revealed that each class of adrenergic receptor has two major subtypes. These are designated by subscripts: a1 and a2 ; b1 and b2 . (There is also a more (b) Axon of Parasympathetic Neuron Synaptic vesicle with acetylcholine (ACh) Figure 9.9 Sympathetic and parasympathetic axons release different neurotransmitters. ( a ) The axons of autonomic neurons have varicosities that form synapses en passant with the target cells. ( b ) In general, sympathetic axons release norepinephrine, which binds to its adrenergic receptors, while parasympathetic neurons release acetylcholine, which binds to its cholinergic receptors (discussed in chapter 7). In most cases, these two neurotransmitters elicit antagonistic responses from smooth muscles. 254 Chapter 9 Table 9.4 | Selected Adrenergic Effects in Different Organs Organ Adrenergic Effects of Sympathoadrenal System Adrenergic Receptor Eye Contraction of radial fibers of the iris dilates the pupils a1 Heart Increase in heart rate and contraction strength b1 primarily Skin and visceral vessels Arterioles constrict due to smooth muscle contraction a1 Skeletal muscle vessels Arterioles constrict due to sympathetic nerve activity a1 Arterioles dilate due to hormone epinephrine b2 Lungs Bronchioles (airways) dilate due to smooth muscle relaxation b2 Stomach and intestine Contraction of sphincters slows passage of food a1 Liver Glycogenolysis and secretion of glucose a1 ,  b2 Source: Simplified from table 6-1, pp. 143–144, of Goodman and Gilman’s The Pharmacological Basis of Therapeutics. Eleventh edition. J.E. Hardman et al., eds. 2006. McGraw-Hill. recently discovered b3 -adrenergic receptor located primarily in adipose tissue, which promotes lipolysis and heat production.) Compounds have been developed that selectively bind to one or the other type of adrenergic receptor and, by this means, either promote or inhibit the normal action produced when epinephrine or norepinephrine binds to the receptor. As a result of its binding to an adrenergic receptor, a drug may either promote or inhibit the adrenergic effect. Also, by using these selective compounds, it has been possible to determine which subtype of adrenergic receptor is present in each organ ( table 9.4 ). All adrenergic receptors act via G-proteins. The action of G-proteins was described in chapter 7, and can be reviewed by reference to figure 7.27 and table 7.6. In short, the binding of epinephrine and norepinephrine to their receptors causes the group of three G-proteins (designated a ,  b , and g ) to dissociate into an a subunit and a bg complex. In different cases, either the a subunit or the bg complex causes the opening or closing of an ion channel in the plasma membrane, or the activation of an enzyme in the membrane. This begins the sequence of events that culminates in the effects of epinephrine and norepinephrine on the target cells. All subtypes of beta receptors produce their effects by stimulating the production of cyclic AMP within the target cells. The response of a target cell when norepinephrine binds to the a1 receptors is mediated by a different secondmessenger system—a rise in the cytoplasmic concentration of Ca 2 1 . This Ca 2 1 second-messenger system is similar, in many ways, to the cAMP system and is discussed together with endocrine regulation in chapter 11 (see fig. 11.10). It should be remembered that each of the intracellular changes following the binding of norepinephrine to its receptor ultimately results in the characteristic response of the tissue to the neurotransmitter. There are different subtypes of a2 -adrenergic receptors that produce different effects. The a2 -adrenergic receptors located on presynaptic axon terminals produce a decreased release of norepinephrine when activated by norepinephrine in the synaptic cleft. This provides negative feedback control over the amount of norepinephrine released. The most medically important subtype of a2 -adrenergic receptors is located in the brain. When these receptors are stimulated by the drug clonidine, they produce a lowering of blood pressure by somehow reducing the activation of the entire sympathoadrenal system. A review of table  9.4 reveals certain generalities about the actions of adrenergic receptors. The stimulation of a1 - adrenergic receptors consistently causes contraction of smooth muscles. We can thus state that the vasoconstrictor effect of sympathetic nerves always results from the activation of alphaadrenergic receptors. The effects of beta-adrenergic activation are more diverse; stimulation of beta-adrenergic receptors promotes the relaxation of smooth muscles (in the digestive tract, bronchioles, and uterus, for example) but increases the force of contraction of cardiac muscle and promotes an increase in cardiac rate. The diverse effects of epinephrine and norepinephrine can be understood in terms of the “fight-or-flight” theme. Norepinephrine released by postganglionic sympathetic axons, and epinephrine released into the blood from the adrenal medulla, boost the ability of the cardiovascular system to respond to physical emergencies. The a -adrenergic receptors are more sensitive to norepinephrine, whereas the b -adrenergic receptors are more sensitive to epinephrine circulating in the blood. Stimulation of b1 - and b2 -adrenergic receptors in the heart increases heart rate and contractility. In the arterioles (small arteries) of the body, a1 -adrenergic receptors stimulate vasoconstriction and b2 -adrenergic receptors promote vasodilation in appropriate organs to prepare the body for physical exertion ( fig. 9.10 ). A drug that binds to the receptors for a neurotransmitter and that promotes the processes that are stimulated by that neurotransmitter is said to be an agonist of that neurotransmitter. A drug that blocks the action of a neurotransmitter, by contrast, is said to be an antagonist. The use of specific drugs that selectively stimulate or block a1 ,  a2 ,  b1 , and b2 receptors has proven extremely useful in many medical applications. Examples of drugs that stimulate (as agonists) and block (as antagonists) adrenergic and cholinergic receptors are provided in table 9.5 . The Autonomic Nervous System

Responses to Cholinergic Stimulation All somatic motor neurons, all preganglionic neurons (sympathetic and parasympathetic), and most postganglionic parasympathetic neurons are cholinergic—they release acetylcholine (ACh) as a neurotransmitter. The effects of ACh released by somatic motor neurons and by preganglionic autonomic neurons are always excitatory. The effects of ACh released by postganglionic parasympathetic axons are usually excitatory, but in some cases they are inhibitory. For example, the cholinergic effect of the postganglionic parasympathetic axons innervating the heart (a part of the vagus nerve) slows the heart rate. It is useful to remember that, in general, the effects of parasympathetic innervation are opposite to the effects of sympathetic innervation. The effects of ACh in an organ depend on the nature of the cholinergic receptor ( fig. 9.11 ). As may be recalled from chapter 7, there are two types of cholinergic receptors—nicotinic and muscarinic. Nicotine (derived from the tobacco plant), as well as ACh, stimulates the nicotinic ACh receptors. These are located in the CNS, neuromuscular junction of skeletal muscle fibers, and in the autonomic ganglia. Nicotinic receptors are thus stimulated by ACh released by somatic motor neurons and by preganglionic autonomic neurons. Muscarine (derived from some poisonous mushrooms), as well as ACh, stimulates the ACh receptors in the visceral organs. Muscarinic receptors are thus stimulated by ACh released by postganglionic parasympathetic axons to produce the parasympathetic effects. Nicotinic and muscarinic receptors are further distinguished by the action of the drugs curare (tubocurarine), which specifically blocks the nicotinic ACh receptors, and atropine (or belladonna ), which specifically blocks the muscarinic ACh receptors. As described in chapter 7, the nicotinic ACh receptors are ligand-gated ion channels. That is, binding to ACh causes the ion channel to open within the receptor protein. This allows Na 1 to diffuse inward and K 1 to diffuse outward. However, the Na 1 gradient is steeper than the K 1 gradient, and so the net effect is a depolarization. As a result, nicotinic ACh receptors are always excitatory. In contrast, muscarinic ACh receptors are coupled to G-proteins, which can then close or open different membrane channels and activate different membrane enzymes. As a result, their effects can be either excitatory or inhibitory ( fig. 9.11 ). Scientists have identified five different subtypes of muscarinic receptors (M 1 through M 5 ; table 9.6 ). Some of these cause contraction of smooth muscles and secretion of glands, while others cause the inhibition that results in a slowing of the heart rate. These actions are mediated by second-messenger systems that will be discussed in more detail in conjunction with hormone action in chapter 11, section 11.2. CLIN ICAL APP LICATI O N Atropine, from the deadly nightshade plant ( Atropa belladonna), is a specific antagonist of the muscarinic ACh receptors, and thus of the effects of postganglionic parasympathetic axons. It is infused on the eyes to inhibit the muscle contraction that constricts the pupils (chapter 10; see fig. 10.28), resulting in pupil dilation for eye exams. Women during the Middle Ages used this effect to make their eyes more attractive (in Italian, bella  5 beautiful,  donna  5 woman). In addition, atropine can be used to block the vagus nerve– induced slowing of the heart, helping to treat bradycardia (a slow heart rate) and AV node heart block. Atropine is used to reduce the production of saliva and mucus (sometimes before general anesthesia), and to inhibit spasmodic contractions of the intestine and the stomach acid secretion of gastritis. Atropine is also used as a treatment for nerve gas and organophosphate pesticide poisoning, because these compounds can inhibit acetylcholinesterase (AChE) to dangerously increase cholinergic transmission. The Autonomic Nervous System 257 Nicotinic ACh receptors Postsynaptic membrane of • All autonomic ganglia • All neuromuscular junctions • Some CNS pathways Na+ ACh Ligand-gated channels (ion channels are part of receptor) K+ Depolarization Muscarinic ACh receptors • Produces parasympathetic nerve effects in the heart, smooth muscles, and glands • G-protein-coupled receptors (receptors influence ion channels by means of G-proteins) ACh α β γ K+ Hyperpolarization (K+ channels opened) ACh Na+ or Ca2+ α β γ K+ Depolarization (K+ channels closed) Excitation Inhibition Produces slower heart rate Excitation Causes smooth muscles of the digestive tract to contract Figure 9.11 Comparison of nicotinic and muscarinic acetylcholine receptors. Nicotinic receptors are ligand-gated, meaning that the ion channel (which runs through the receptor) is opened by binding to the neurotransmitter molecule (the ligand). The muscarinic ACh receptors are G-protein-coupled receptors, meaning that the binding of ACh to its receptor indirectly opens or closes ion channels through the action of G-proteins. Table 9.6 | Cholinergic Receptors and Responses to Acetylcholine ReceptorTissueResponseMechanisms Nicotinic Skeletal muscle Depolarization, producing action potentials and muscle contraction ACh opens cation channel in receptor Nicotinic Autonomic ganglia Depolarization, causing activation of postganglionic neurons ACh opens cation channel in receptor Muscarinic ( M 3 ,  M 5 ) Smooth muscle, glands Depolarization and contraction of smooth muscle, secretion of glands ACh activates G-protein coupled receptor, opening Ca 2 1 channels and increasing cytosolic Ca 2 1 Muscarinic ( M 2 ) Heart Hyperpolarization, slowing rate of spontaneous depolarization ACh activates G-protein coupled receptor, opening channels for K 1 Source: Simplified from table 6-2, p. 119, of Goodman and Gilman’s The Pharmacological Basis of Therapeutics. Ninth edition. J.E. Hardman et al., eds. 1996 and

Organs with Dual Innervation Most visceral organs receive dual innervation —they are innervated by both sympathetic and parasympathetic fibers. In this condition, the effects of the two divisions of the autonomic system may be antagonistic, complementary, or cooperative ( table 9.7 ). Antagonistic Effects The effects of sympathetic and parasympathetic innervation of the pacemaker region of the heart is the best example of the antagonism of these two systems. In this case, sympathetic and parasympathetic fibers innervate the same cells. Adrenergic stimulation from sympathetic fibers increases the heart rate, whereas the release of acetylcholine from parasympathetic fibers decreases the heart rate. The heart rate is thereby increased when (1) sympathetic nerve activity remains constant and parasympathetic activity decreases (the level of parasympathetic activity most affects the resting heart rate and early increases in heart rate); and (2) sympathetic nerve activity increases (during more intense exercise). A reverse of this antagonism is seen in the digestive tract, where sympathetic nerves inhibit and parasympathetic nerves stimulate intestinal movements and secretions. The effects of sympathetic and parasympathetic stimulation on the diameter of the pupil of the eye are analogous to the reciprocal innervation of flexor and extensor skeletal muscles by somatic motor neurons (chapter 12, section 12.5). This is because the iris contains antagonistic muscle layers. Contraction of the radial muscles, which are innervated by sympathetic nerves, causes dilation; contraction of the circular muscles, which are innervated by parasympathetic nerve endings, causes constriction of the pupils (chapter 10, fig. 10.28). Complementary and Cooperative Effects The effects of sympathetic and parasympathetic nerves are generally antagonistic; in a few cases, however, they can be complementary or cooperative. The effects are complementary when sympathetic and parasympathetic stimulation produce similar effects. The effects are cooperative when sympathetic and parasympathetic stimulation produce different effects that work together to promote a single action. The effects of sympathetic and parasympathetic stimulation on salivary gland secretion are complementary. The secretion of watery saliva is stimulated by parasympathetic nerves, which also stimulate the secretion of other exocrine glands in the digestive tract. Sympathetic nerves stimulate the constriction of blood vessels throughout the digestive tract. The resultant decrease in blood flow to the salivary glands causes the production of a thicker, more viscous saliva. The effects of sympathetic and parasympathetic stimulation on the reproductive system are cooperative. Erection of the penis, for example, is due to vasodilation resulting from parasympathetic nerve stimulation; ejaculation is due to stimulation through sympathetic nerves. The two divisions of the autonomic system thus cooperate to enable sexual function in the male. They also cooperate in the female; clitoral erection and vaginal secretions are stimulated by parasympathetic nerves, whereas orgasm is a sympathetic nerve response, as it is in the male. There is also cooperation between the two divisions in the micturition (urination) reflex. Although the contraction of the urinary bladder is largely independent of nerve stimulation, it is promoted in part by the action of parasympathetic nerves. This is exploited clinically in helping people with incontinence (involuntary urination) caused by overactive bladder. In this condition, contractions of the detrusor muscle (of the urinary bladder; chapter 17, section 17.1) are stimulated by ACh released by parasympathetic axons. Newer drugs ( darifenacin and solifenacin ) are available to block the specific muscarinic receptor subtypes (primarily M 3 ) that mediate the parasympathetic stimulation of bladder contractions. The control of micturition requires cooperation with the sympathetic division, which has antagonistic effects to the The Autonomic Nervous System 259 Table 9.7 | Adrenergic and Cholinergic Effects of Sympathetic and Parasympathetic Nerves Effect of Sympathetic Parasympathetic Organ Action Receptor *Action Receptor * Eye Iris Radial muscle Contracts (dilates pupil) a1 — — Circular muscle — — Contracts (constricts pupil) M Heart Sinoatrial node Increases heart rate b1 Decreases heart rate M Contractility Increases b1 Decreases (atria) M Vascular Smooth Muscle Skin, splanchnic vessels Contracts (vasoconstriction) a , b — — Skeletal muscle vessels Relaxes (vasodilation) b2 — — Relaxes (vasodilation) M **— — Bronchiolar Smooth Muscle Relaxes (bronchodilation) b2 Contracts (bronchoconstriction) M Gastrointestinal Tract Smooth muscle Walls Relaxes b2 Contracts M Sphincters Constricts a1 Relaxes M Secretion Inhibits a2 Stimulates M Myenteric plexus Inhibits a — — Genitourinary Smooth Muscle Bladder wall (detrussor m.) Relaxes slightly b2 Contracts M Urethral sphincter Contracts a1 Relaxes M Uterus, pregnant Relaxes b2 — — Contracts a1 — — Penis Ejaculation a1 Erection M Skin Pilomotor smooth muscle Contracts a1 — — Sweat glands Thermoregulatory Increases M — — Apocrine (stress) in palms Increases a1 — — *Adrenergic receptors are indicated as alpha ( a ) or beta ( b ); cholinergic receptors are indicated as muscarinic (M). **Vascular smooth muscle in skeletal muscle has sympathetic cholinergic dilator fibers. Source: Reproduced and modified, with permission, from Katzung, B.G.: Basic and Clinical Pharmacology, 6th edition, copyright Appleton & Lange, Norwalk, CT, 1995, with modifications from Goodman & Gilman’s The Pharmalogical Basis of Therapeutics, Eleventh edition, 2006, McGraw-Hill. 260 Chapter 9 parasympathetic division on the internal urethral sphincter. This smooth muscle, together with the external urethral sphincter (composed of skeletal muscle), guards the exit of the bladder to the urethra. When parasympathetic nerve activity to the detrusor muscle of the bladder increases to stimulate bladder contraction, sympathetic activity to the internal sphincter muscle must decrease to allow the sphincter to relax and the bladder to empty. Voluntary control of micturition is discussed in chapter 17, section 17.1.

Control of the Autonomic Nervous System by Higher Brain Centers Visceral functions are largely regulated by autonomic reflexes. In most autonomic reflexes, sensory input is transmitted to brain centers that integrate this information and respond by modifying the activity of preganglionic autonomic neurons. The neural centers that directly control the activity of autonomic nerves are influenced by higher brain areas, as well as by sensory input. The medulla oblongata of the brain stem controls many activities of the autonomic system. Almost all autonomic responses can be elicited by experimental stimulation of the medulla, where centers for the control of the cardiovascular, pulmonary, urinary, reproductive, and digestive systems are located. Much of the sensory input to these centers travels in the afferent fibers of the vagus nerve—a mixed nerve containing both sensory and motor fibers. The reflexes that result are listed in table 9.8 . Although it directly regulates the activity of autonomic motor fibers, the medulla itself is responsive to regulation by higher brain areas. One of these areas is the hypothalamus, the brain region that contains centers for the control of body temperature, hunger, and thirst; for regulation of the pituitary gland; and (together with the limbic system and cerebral cortex) for various emotional states. Because several of these functions involve appropriate activation of sympathetic and parasympathetic nerves, many scientists consider the hypothalamus to be the major regulatory center of the autonomic system. The Autonomic Nervous System 261 Table 9.8 | Sensory Receptors Stimulate Afferent Fibers in the Vagus, Which Transmit to the Medulla Oblongata and Cause Autonomic Reflexes OrgansType of ReceptorsReflex effects Lungs Stretch receptors Further inhalation inhibited; increase in cardiac rate and vasodilation stimulated Type J receptors Stimulated by pulmonary congestion—produces feelings of breathlessness and causes a reflex fall in cardiac rate and blood pressure Aorta Chemoreceptors Stimulated by rise in CO 2 and fall in O 2 —produces increased rate of breathing, rise in heart rate, and vasoconstriction Baroreceptors Stimulated by increased blood pressure—produces a reflex decrease in heart rate Heart Atrial stretch receptors Antidiuretic hormone secretion inhibited, thus increasing the volume of urine excreted Stretch receptors in ventricles Produces a reflex decrease in heart rate and vasodilation Gastrointestinal tract Stretch receptors Feelings of satiety, discomfort, and pain The limbic system is a group of fiber tracts and nuclei that form a ring around the brain stem (chapter 8, section 8.2). It includes the cingulate gyrus of the cerebral cortex, the hypothalamus, the fornix (a fiber tract), the hippocampus, and the amygdaloid nucleus (see fig. 8.15). The limbic system is involved in basic emotional drives, such as anger, fear, sex, and hunger. The involvement of the limbic system with the control of autonomic function is responsible for the visceral responses that are characteristic of these emotional states. Blushing, pallor, fainting, breaking out in a cold sweat, a racing heartbeat, and “butterflies in the stomach” are only some of the many visceral reactions that accompany emotions as a result of autonomic activation. The autonomic correlates of motion sickness—nausea, sweating, and cardiovascular changes—are eliminated by cutting the motor tracts of the cerebellum. This demonstrates that impulses from the cerebellum to the medulla oblongata influence activity of the autonomic nervous system. Experimental and clinical observations have also demonstrated that the frontal and temporal lobes of the cerebral cortex influence lower brain areas as part of their involvement in emotion and personality. Studies indicate that aging is associated with increased levels of sympathetic nervous system activity. This represents an increased level of tonic sympathetic tone in healthy adults, not an increased response to stress. It has been suggested that the higher tonic levels of sympathetic nerve activity may promote increased catabolism, generating heat and helping to combat the greater amounts of adipose tissue in the elderly. However, chronically elevated sympathetic tone may increase the risk of hypertension and cardiovascular diseases. CLIN ICAL APP LICATI O N The somatic motor system is clearly under voluntary control, whereas the autonomic nervous system operates without conscious involvement. However, scientists have verified that, using biofeedback techniques, a person can be trained to have limited but significant control over some autonomic responses. This training involves the use of devices that monitor body changes; for example, devices can monitor brain waves (electroencephalograph or EEG), muscle tension (electromyography, or EMG), skin conductivity (affected by sweating and monitored by GSR—galvanic skin response), and others. Autonomic functions may be trained to help control blood pressure, chronic pain, headache, urinary incontinence, anxiety, and other conditions. Clinical Investigation CLUES Sofia monitored her pulse rate in an attempt to calm her anxiety. • How does the autonomic system control the pulse rate? • What technique is she employing, and can it work?

Autonomic dysreflexia is a serious condition that can cause stroke, pulmonary edema, and myocardial infarction (heart attack) in people with spinal cord injuries at or above the sixth thoracic level (T6) of the spinal cord. Spinal shock may occur immediately after a spinal cord injury, especially if the cord is completely transected. At first there is a loss of spinal reflexes below the level of the injury, but after some time the reflexes reappear in an exaggerated state. In this condition, a noxious sensory stimulus—usually from the urinary bladder or colon—can evoke a strong response from the sympathoadrenal system. Sympathetic nerves cause vasoconstriction and increased heart rate, which raise the blood pressure. Pressure receptors in arteries sense this, and send signals via cranial nerves IX and X to the brain (chapter 14; see fig. 14.27). In response, the brain directs an inhibition of sympathetic activity and an increase in parasympathetic activity, which normally maintain homeostasis. However, if the person has a spinal cord injury at or above T6, the inhibition of the sympathetic (thoracolumbar) response cannot descend below the injury. High sympathetic nerve activity is maintained below the level of the injury, producing vasoconstriction that can cause dangerous hypertension as well as a cold skin and goose bumps. By contrast, sympathetic nerve activity is decreased above the level of the injury, accompanied by increased parasympathetic nerve effects. This results in bradycardia (a slow heart rate), nasal congestion, and a flushed, sweaty skin above the level of the spinal cord injury. The bradycardia is insufficient to lower the dangerously elevated blood pressure, and so autonomic dysreflexia requires efforts to eliminate the noxious stimulus that provok

vaxtang lagvilava shared a form Header profile photo vaxtang lagvilava (v.lagvilava@seu.edu.ge) has invited you to respond to the following form: Body Function IV (Week 8) Snapshot of the item below: Google Forms Having trouble viewing or submitting this form? Fill out in Google Forms . Body Function IV (Week 8) Molecular aspects of hormonal regulation. Portal ID Which structure secretes releasing hormones in the hormonal cascade? A. Hypothalamus B. Anterior pituitary C. Adrenal cortex D. Thyroid gland Releasing hormones primarily stimulate the: A. Target endocrine glands B. Posterior pituitary C. Anterior pituitary D. Peripheral tissues Which hormone is synthesized in the adrenal medulla from tyrosine? A. Cortisol B. Epinephrine C. Aldosterone D. Progesterone Thyroid hormones are synthesized by incorporation of iodine into: A. Cholesterol B. Tryptophan C. Tyrosine residues of thyroglobulin D. Histidine Protein hormones act mainly through: A. Nuclear receptors B. Cytoplasmic receptors C. Cell surface receptors D. Mitochondrial receptors Which second messenger is commonly activated by peptide hormones? A. Cyclic AMP B. Cholesterol C. Cortisol D. Thyroxine Gonadotropin-releasing hormone (GnRH) is secreted from the: A. Ovary B. Hypothalamus C. Pituitary gland D. Adrenal gland GnRH stimulates secretion of: A. ACTH and TSH B. Cortisol and aldosterone C. Estrogen and progesterone D. FSH and LH Binding of insulin to its receptor activates: A. DNA polymerase B. Auto-tyrosine kinase C. Adenylate cyclase inhibition D. Phospholipase degradation Steroid hormones are derived from: A. Tyrosine B. Glycine C. Cholesterol D. Histamine Aldosterone is synthesized in the: A. Adrenal cortex B. Adrenal medulla C. Thyroid gland D. Pituitary gland Testosterone is mainly produced by: A. Follicular cells B. Leydig cells C. Lactotrophs D. Corticotrophs Steroid hormones circulate bound to plasma proteins mainly to: A. Increase degradation B. Increase excretion C. Protect from degradation D. Inhibit receptor binding Steroid hormone receptors function primarily as: A. Ion channels B. Transport proteins C. Enzymes D. Ligand-activated transcription factors Which hormone uses an intracellular receptor? A. Insulin B. Glucagon C. Cortisol D. Epinephrine The DNA-binding domain is a feature of: A. Steroid hormone receptors B. GPCRs C. Ion channels D. Enzyme-linked receptors only Which hormone category includes insulin? A. Steroid hormone B. Catecholamine C. Thyroid hormone D. Peptide hormone Catecholamines are derived from: A. Cholesterol B. Tyrosine C. Glycine D. Tryptophan Endocrine hormones reach target cells through the: A. Lymphatic system only B. Interstitial fluid only C. General circulation D. Synaptic clefts A hormone acting on neighboring cells is called: A. Endocrine B. Autocrine C. Intracrine D. Paracrine Autocrine hormones act on: A. Distant organs B. The same cell that secretes them C. Only neurons D. Blood vessels only Hormonal cascades amplify signals by: A. Decreasing hormone concentration B. Reducing receptor numbers C. Producing increasing amounts of hormone at successive levels D. Preventing hormone secretion Corticotropin-releasing hormone (CRH) is secreted by the: A. Adrenal cortex B. Hypothalamus C. Thyroid gland D. Pancreas CRH stimulates release of: A. ACTH B. TSH C. FSH D. GH ACTH acts mainly on the: A. Thyroid gland B. Adrenal cortex C. Ovaries D. Testes ACTH stimulates secretion of: A. Insulin B. Thyroxine C. Cortisol D. Estrogen Cortisol exerts feedback inhibition on: A. Hypothalamus and anterior pituitary B. Adrenal medulla only C. Pancreas only D. Thyroid gland only Long-loop feedback involves: A. Releasing hormone inhibition only B. Ultimate hormone inhibiting higher centers C. Self-inhibition of releasing hormone D. Pituitary inhibition of target gland Short-loop feedback is exerted by: A. Target gland hormone B. Ultimate hormone only C. Pituitary tropic hormone D. Neurotransmitters Ultrashort feedback involves: A. Hormone acting on its own hypothalamic cells B. Adrenal cortex feedback C. Thyroid gland feedback D. Ovarian feedback Vasopressin is synthesized mainly in the: A. Paraventricular nucleus B. Supraoptic nucleus C. Pituitary gland D. Pineal gland Oxytocin is synthesized mainly in the: A. Supraoptic nucleus B. Thyroid gland C. Paraventricular nucleus D. Adrenal gland Oxytocin and vasopressin are stored in the: A. Anterior pituitary B. Posterior pituitary C. Thyroid gland D. Adrenal medulla Dopamine and serotonin help regulate secretion of: A. Releasing hormones B. Steroid hormones only C. Thyroid hormones only D. Cortisol only Pulsatile release of GnRH is regulated by: A. Aminergic neurons B. Thyroid follicles C. Leydig cells D. Adrenal cortex Rhythmic cyclic secretion of cortisol is influenced by: A. Aminergic neuronal activity B. Follicular cells C. Osteoblasts D. Chondrocytes Growth hormone is secreted by the: A. Anterior pituitary B. Posterior pituitary C. Thyroid gland D. Adrenal medulla Thyroid-stimulating hormone is also known as: A. LH B. ACTH C. TSH D. GH ACTH stands for: A. Adrenocorticotropic hormone B. Antithyroid hormone C. Adenocortical hormone D. Adrenal thyroid hormone β-Endorphin is produced by: A. Pars intermedia-like cells B. Thyroid follicles C. Leydig cells D. Ovarian follicles Which hormone is classified as a catecholamine? A. Cortisol B. Progesterone C. Epinephrine D. Aldosterone Which hormone is classified as a steroid hormone? A. ACTH B. Cortisol C. Insulin D. GH Which hormone is produced by the ovaries? A. Estrogen B. ACTH C. TSH D. CRH Which messenger activates protein kinases in target cells? A. Second messenger B. Cholesterol C. Hemoglobin D. Albumin The ligand-binding domain of steroid receptors is located at the: A. N-terminus B. DNA-binding region C. Carboxy-terminus D. Membrane region The ovarian cycle is controlled by secretion of: A. GnRH B. ACTH C. CRH D. Vasopressin Which hormone has a longer half-life than ACTH? A. CRH B. Cortisol C. GnRH D. Dopamine Cells respond to hormones according to the number of: A. Ribosomes B. Lysosomes C. Receptors expressed D. Mitochondria Which hormone is released in microgram amounts during the CRH-ACTH-cortisol cascade? A. CRH B. ACTH C. Cortisol D. Estrogen Which hormone is released in milligram amounts in the hormonal cascade example? A. CRH B. ACTH C. GnRH D. Cortisol Proopiomelanocortin (POMC) is the precursor of: A. Insulin B. ACTH C. Thyroxine D. Aldosterone Vasopressin and oxytocin are synthesized initially as: A. Active hormones B. Steroid precursors C. Preprohormones D. Catecholamines Neurophysins are: A. Steroid hormones B. Carrier proteins produced with ADH and oxytocin C. Enzymes of thyroid synthesis D. Receptors for vasopressin Which hormone is NOT derived from POMC? A. ACTH B. β-Endorphin C. α-MSH D. Oxytocin In humans, the pars intermedia: A. Is a large distinct lobe B. Is absent completely C. Exists mainly as residual pars intermedia-like cells D. Produces only TSH Vasopressin is released in response to: A. Increased blood pressure only B. Decreased blood pressure and increased osmolarity C. Decreased sodium concentration D. Increased insulin levels Oxytocin is responsible for: A. Glucose uptake B. Thyroid hormone synthesis

vaxtang lagvilava shared a form Header profile photo vaxtang lagvilava (v.lagvilava@seu.edu.ge) has invited you to respond to the following form: Bio II (Lesson VIII) Snapshot of the item below: Google Forms Having trouble viewing or submitting this form? Fill out in Google Forms . Bio II (Lesson VIII) Acetylcholine (ACh) in the CNS is mainly involved in: A. Pain reflexes B. Cognitive processes C. Visual acuity D. Muscle hypertrophy after release into the synaptic cleft, ACh is rapidly degraded by: A. Monoamine oxidase B. Catechol-O-methyltransferase C. Acetylcholinesterase D. Choline acetyltransferase The high-affinity choline transporter responsible for choline reuptake into cholinergic terminals is: A. VAChT B. CHT1 C. DAT D. NET New evidence suggests that ACh can: A. Only act on plasma membrane receptors B. Be transported into postsynaptic neurons C. Be synthesized postsynaptically D. Inhibit dopamine release directly Intracellular M1 muscarinic receptors are prominently located in the: A. Nucleus only B. Golgi apparatus C. Lysosomes D. Synaptic vesicles Among muscarinic receptor subtypes, the most abundant in the CNS is: A. M1 B. M3 C. M2 D. M5 Surface M1 mAChRs primarily mediate: A. ERK activation over minutes B. PIP2 hydrolysis and rapid Ca²⁺ increase C. Gene transcription D. Protein synthesis Intracellular M1 receptors mainly activate: A. PIP2 pathway B. cAMP pathway C. ERK1/2 pathway D. Dopamine signaling Early-phase LTP is mainly associated with: A. ERK activation B. Gene transcription C. Rapid Ca²⁺ elevation D. Protein degradation Late-phase LTP depends primarily on: A. Sodium influx B. MAPK/ERK cascade C. Immediate membrane depolarization D. Acetylcholine hydrolysis M1 knockout mice show deficits in: A. Vision B. Working memory C. Hearing D. Motor reflexes only The main nicotinic receptor subtype highly permeable to Ca²⁺ is: A. α1 B. M2 C. β1 D. α7 Intracellular nicotinic receptors have been identified in: A. Lysosomes B. Mitochondria C. Ribosomes D. Microtubules ACh uptake into postsynaptic neurons is: A. Passive diffusion B. Mediated by a proposed ACh transporter C. Voltage-gated D. Dependent on dopamine ACh uptake is temperature-dependent, suggesting: A. Diffusion B. Enzymatic degradation C. Active transport D. Vesicular exocytosis ACh uptake is inhibited by: A. Glutamate B. GABA C. Hemicholinium-3 (HC-3) D. Dopamine Clinically used AChE inhibitors include: A. Fluoxetine B. Donepezil C. Haloperidol D. Diazepam Presynaptic muscarinic autoreceptors mainly involved in autoinhibition are: A. M2 B. M1 C. M3 D. M5 Blocking presynaptic mAChRs with atropine results in: A. Reduced ACh release B. Increased ACh release C. No change D. Dopamine suppression HC-3 at low concentrations selectively inhibits: A. ACh uptake B. M2 receptors C. CHT1 D. AChE Physiological plasma choline concentration is approximately: A. 1–2 μM B. 5–7 μM C. 10–50 μM D. 100 μM The early facilitation of NMDAR-dependent LTP is mediated mainly by: A. Intracellular M1 B. Surface M1 C. M2 receptors D. α7 nAChRs Dopamine is converted to norepinephrine by: A. Tyrosine hydroxylase B. Monoamine oxidase C. Dopamine-β-hydroxylase D. PNMT Dopamine-β-hydroxylase (DBH) is located primarily in the: A. Cytoplasm only B. Synaptic vesicles C. Nucleus D. Mitochondria DBH requires which metal ions for activity? A. Iron B. Zinc C. Copper D. Magnesium DBH is also known as: A. Catechol-O-methyltransferase B. Dopamine β-monooxygenase C. Aromatic L-amino acid decarboxylase D. Aldehyde reductase The electron donor used by DBH during hydroxylation is: A. NADH B. FAD C. Ascorbic acid D. ATP PNMT catalyzes the conversion of norepinephrine to: A. Dopamine B. Epinephrine C. DHPG D. DOPAC PNMT uses which methyl donor? A. ATP B. NADPH C. S-adenosylmethionine (SAM) D. FAD PNMT is best described as a: A. Membrane-bound dimer B. 30 kDa soluble monomer C. Tetrameric enzyme D. Mitochondrial enzyme DAT and NET are located: A. Directly in the synaptic cleft B. On postsynaptic membranes C. Outside the synaptic cleft D. In the nucleus Dopamine is primarily metabolized by MAO into: A. DHPG B. MHPG C. DOPAC D. VMA Norepinephrine is primarily converted to: A. DOPAC B. DHPG C. Dopamine D. Epinephrine The β-hydroxyl group on norepinephrine favors metabolism via: A. MAO only B. COMT only C. Aldehyde reductase D. TH DHPG is further metabolized by COMT to: A. VMA B. MHPG C. DOPAC D. HVA The major urinary metabolite of norepinephrine and epinephrine in humans is: A. DOPAC B. MHPG C. VMA D. DHPG All adrenergic receptors belong to which receptor class? A. Ionotropic receptors B. GPCRs C. Nuclear receptors D. Enzyme-linked receptors Adrenergic receptors contain how many transmembrane domains? . 6 C. 7 D. 8 α1-adrenergic receptors are coupled to: A. Gi B. Gs C. Gq D. Gt α2-adrenergic receptors are coupled to: A. Gq B. Gi C. Gs D. Golf β1–3 adrenergic receptors are coupled to: A. Gi B. Gq C. Gs D. G12 Powered by Google Forms This form was created inside of Georgian National University SEU. Report Abuse - Terms of Service - Additional Terms Create your own Google Form Google LLC, 1600 Amphitheatre Parkway, Mountain View, CA 94043, USA You have received this email because v.lagvilava@seu.edu.ge shared a file or folder located in Google Drive with you.