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Cholecystokinin-Pancreozymin (CCK-PZ)

MBBS 1st Year Physiology Notes

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1. Historical Background

• Cholecystokinin (CCK) was first described by Ivy and Oldberg (1928) as a hormone causing gallbladder contraction.
• Pancreozymin (PZ) was separately identified by Harper and Raper (1943) as a hormone stimulating pancreatic enzyme secretion.
• Later proved to be the same molecule — hence the dual name CCK-PZ.
• Now commonly called simply CCK.

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2. Chemical Nature & Structure

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3. Source / Site of Secretion

• I cells (also called Ito cells) of the duodenal and proximal jejunal mucosa
• Also found in:
  • Neurons of the enteric nervous system (acts as neurotransmitter)
  • Brain (hypothalamus, cerebral cortex) — mediates satiety

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4. Stimuli for Release

✅ Stimulatory Factors:

❌ Inhibitory Factors:

• Somatostatin — inhibits CCK release
• CCK-releasing factor (CCK-RF) is inactivated by trypsin and chymotrypsin in the duodenum — so when proteases are present (i.e., after eating protein), they stop further CCK release (negative feedback)
• Pancreatic proteases (feedback inhibition)

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5. Mechanism of Action

• Acts via CCK-A receptors (alimentary/peripheral) and CCK-B receptors (brain/gastric, also respond to gastrin)
• Second messenger: IP₃ / Ca²⁺ pathway (Phospholipase C → DAG + IP₃)
• Important human-specific note (Harrison's p.9714): Unlike other species, there are no CCK receptors on acinar cells in humans. In humans, CCK at physiologic concentrations stimulates pancreatic secretion by stimulating afferent vagal and intrapancreatic nerves — i.e., it acts indirectly via the vagus nerve.

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6. Actions of CCK-PZ

A. 🫀 On the Gallbladder (the "Cholecysto-" part)

1. Powerful contraction of the gallbladder → bile expelled into duodenum
2. Relaxation of the Sphincter of Oddi → decreased resistance to bile flow
3. Enhanced flow of biliary contents into the duodenum
4. Facilitates digestion of fats and fat-soluble vitamins

B. 🫁 On the Pancreas (the "-kinin/Pancreozymin" part)

1. Stimulates enzyme-rich (ecbolic) secretion from acinar cells
   • Amylase, lipase, proteases (trypsinogen, chymotrypsinogen, etc.)
2. Acts via vagal pathways (not directly on acinar cells in humans)
3. Potentiates secretin's action on bicarbonate secretion (synergism)

C. 🧠 On the Brain (Satiety)

1. Acts on hypothalamus via CCK-B receptors
2. Produces satiety (feeling of fullness) — reduces food intake
3. This is why high-fat/high-protein meals make you feel full quickly

D. 🔄 On the Stomach

1. Weak stimulation of gastric acid secretion (via CCK-B receptors shared with gastrin)
2. Slows gastric emptying — allows adequate time for digestion in the duodenum

E. 🧫 On the Intestine

1. Stimulates intestinal motility
2. Enhances growth of exocrine pancreas (trophic effect)

F. On Sphincter of Oddi

• Relaxes the sphincter → promotes bile and pancreatic juice flow into duodenum

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7. Summary of Actions Table

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8. Phases of Pancreatic Secretion & CCK Role

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9. CCK vs. Secretin — Key Comparison

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10. Clinical Correlates (High Yield for Exams)

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11. CCK as a Neurotransmitter

• CCK-8 is the most abundant neuropeptide in the CNS
• Found in cortex, hippocampus, hypothalamus
• Functions:
  • Satiety signaling
  • Anxiety modulation
  • Pain modulation
  • Memory and learning

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12. Quick Revision Points (Memory Aids)

• "CCK = Contract, Contract, Kill acid, Kinin enzymes"
  • Contracts gallbladder
  • Cuts (relaxes) Sphincter of Oddi
  • Kills hunger (satiety)
  • Kindles pancreatic enzyme secretion
• Cells: I cells (I = "I" make you full and digest fat)
• Stimuli: Fat and Protein → best stimuli
• CCK-8: most biologically active form

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13. Diagram — CCK in Food-Intake & Metabolic Regulation

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References

• Harrison's Principles of Internal Medicine, 21st Edition, pp. 9657, 9712, 9714
• Ganong's Review of Medical Physiology
• Guyton & Hall Textbook of Medical Physiology