A 19-year-old man presents with polyuria and polydipsia. Serum sodium is 148 mEq/L, urine osmolality is 110 mOsm/kg, and urine osmolality fails to rise after desmopressin administration. Desmopressin normally produces its antidiuretic effect through which signalling sequence?
- A V1 receptor, Gq, IP3-mediated calcium release
- B V2 receptor, Gi, inhibition of adenylate cyclase
- C V2 receptor, Gs, cAMP-dependent insertion of aquaporin-2 into the collecting duct apical membrane ✓
- D Direct activation of guanylyl cyclase and PKG
Correct answer: C. V2 receptor, Gs, cAMP-dependent insertion of aquaporin-2 into the collecting duct apical membrane
Explanation
Antidiuresis uses the V2 receptor, a Gs-coupled GPCR on collecting duct principal cells. cAMP activates PKA, which promotes trafficking of preformed aquaporin-2 vesicles to the apical membrane, allowing water reabsorption. Failure to concentrate urine after exogenous desmopressin indicates nephrogenic diabetes insipidus, caused by V2 receptor or aquaporin-2 defects. The V1 receptor with Gq and calcium mediates vasoconstriction, not water reabsorption, which kills distractor A.
Reference: Ganong's Review of Medical Physiology, 26th ed.
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