Aquaporin-2 (AQP2) water channels are regulated by ADH (vasopressin) in the collecting duct. The intracellular signaling cascade linking V2 receptor activation to AQP2 membrane insertion is:

• A V2R → Gs → adenylyl cyclase → cAMP → PKA → AQP2 phosphorylation at Ser256 → exocytosis to apical membrane ✓
• B V2R → Gq → phospholipase C → IP3 → Ca²⁺ release → calmodulin-kinase II → AQP2 translocation
• C V2R → Gi → inhibits adenylyl cyclase → decreased cAMP → PKG activation → AQP2 endocytosis
• D V2R → β-arrestin → ERK1/2 → MAPK pathway → de novo AQP2 synthesis within 30 minutes

Explanation

The V2 (vasopressin type 2) receptor couples to Gs protein, activating adenylyl cyclase to generate cAMP, which activates protein kinase A (PKA). PKA phosphorylates AQP2 at serine-256, triggering fusion of AQP2-containing vesicles with the apical membrane (exocytosis), dramatically increasing water permeability. This is the 'shuttle hypothesis.' Conversely, removal of ADH leads to dephosphorylation and endocytosis of AQP2. Nephrogenic diabetes insipidus results from V2R mutations or AQP2 mutations impairing this cascade.

Reference: Guyton & Hall, Textbook of Medical Physiology, 14th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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