A patient with a VIPoma (Verner-Morrison syndrome) presents with profuse watery diarrhoea, hypokalaemia, and achlorhydria (WDHA syndrome). VIP acts on intestinal epithelial cells via which mechanism to cause secretory diarrhoea?
- A VIP activates Gq-coupled receptors → ↑IP3 → Ca2+-mediated Cl- channel opening
- B VIP activates Gs-coupled VPAC receptors → ↑cAMP → PKA phosphorylates CFTR → Cl- secretion into lumen (and passive water and Na+ secretion) ✓
- C VIP inhibits Na+/K+-ATPase on basolateral surface, reducing Na+ absorption
- D VIP stimulates histamine release from enterochromaffin cells, which activates H2 receptors on enterocytes
Correct answer: B. VIP activates Gs-coupled VPAC receptors → ↑cAMP → PKA phosphorylates CFTR → Cl- secretion into lumen (and passive water and Na+ secretion)
Explanation
VIP (vasoactive intestinal peptide) binds VPAC1/VPAC2 receptors (Gs-coupled GPCRs) on intestinal epithelial cells, activating adenylyl cyclase and raising cAMP. PKA then phosphorylates CFTR (cystic fibrosis transmembrane conductance regulator), activating this apical Cl- channel and driving Cl- secretion. Na+ and water follow paracellularly into the lumen, causing massive secretory diarrhoea. VIP also inhibits gastric acid secretion (explaining achlorhydria) and causes splanchnic vasodilation. Elevated serum VIP > 200 pg/mL confirms the diagnosis.
Reference: Guyton & Hall, Textbook of Medical Physiology, 14th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
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