Parietal cells secrete HCl via the H⁺-K⁺-ATPase. The stimulation of acid secretion by histamine involves H2 receptors that activate Gs → adenylyl cyclase → cAMP → PKA. Which additional pathway, activated simultaneously by acetylcholine and gastrin, synergistically amplifies acid secretion?
- A Gi-coupled M2 muscarinic receptors → adenylyl cyclase inhibition → cAMP reduction → paradoxical acid stimulation
- B Beta-2 adrenoceptors on parietal cells → Gs → cAMP → synergistic effect with histamine
- C Both acetylcholine and gastrin act via Gs to additively increase cAMP, which is the sole second messenger for acid secretion
- D Gq-coupled M3 muscarinic and CCK2 receptors → phospholipase C → IP3/DAG → Ca²⁺/PKC → H⁺-K⁺-ATPase insertion and activation ✓
Correct answer: D. Gq-coupled M3 muscarinic and CCK2 receptors → phospholipase C → IP3/DAG → Ca²⁺/PKC → H⁺-K⁺-ATPase insertion and activation
Explanation
Parietal cell acid secretion is regulated by three parallel pathways. Histamine via H2 receptor/Gs/cAMP/PKA and acetylcholine via M3/Gq/IP3-Ca²⁺/PKC and gastrin via CCK2/Gq/IP3-Ca²⁺/PKC. The Ca²⁺ and PKC pathways stimulate translocation of tubulovesicular H⁺-K⁺-ATPase to the apical canalicular membrane. Synergism occurs because cAMP and Ca²⁺ pathways converge on the same exocytotic machinery; their combination produces far greater acid output than either alone. Proton pump inhibitors irreversibly block H⁺-K⁺-ATPase regardless of which pathway is activated.
Reference: Guyton & Hall, Textbook of Medical Physiology, 14th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
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