The cephalic phase of gastric acid secretion is abolished by vagotomy. Which intracellular mechanism in parietal cells mediates the muscarinic (M3) component of vagal stimulation?
- A M3 → Gs → cAMP → PKA → activation of H⁺/K⁺-ATPase (same pathway as histamine H2)
- B M3 → Gq → PLC → IP3/DAG → IP3 releases Ca²⁺ from ER and DAG activates PKC → activation of H⁺/K⁺-ATPase insertion into apical membrane ✓
- C M3 → Gi → reduced cAMP → disinhibition of somatostatin pathway → net acid increase
- D M3 → β-arrestin → MAPK → acid secretion independent of second messengers
Explanation
Parietal cells have three stimulatory receptors: M3 (muscarinic), H2 (histamine), and CCK-B/gastrin receptors. M3 and CCK-B are Gq-coupled: activation generates IP3 (releases Ca²⁺ from ER) and DAG (activates PKC). Ca²⁺/PKC signaling triggers translocation of tubulovesicles containing H⁺/K⁺-ATPase to the apical (canalicular) membrane, dramatically increasing its surface area and acid output. H2 receptors use the Gs-cAMP-PKA pathway, which also triggers H⁺/K⁺-ATPase insertion. All three pathways converge on proton pump membrane insertion; this explains why PPIs (blocking the pump directly) are superior to H2 blockers alone.
Reference: Guyton & Hall, Textbook of Medical Physiology, 14th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
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