A patient with central diabetes insipidus is given DDAVP and responds with concentrated urine. The V2 receptor activated by DDAVP in principal cells of the collecting duct operates through which intracellular signalling cascade to insert aquaporin-2 (AQP2) into the apical membrane?

• A Gq → phospholipase C → IP3 → intracellular Ca²⁺ release → calcineurin → AQP2 dephosphorylation
• B Gi → inhibition of adenylyl cyclase → reduced cAMP → reduced PKA → redistribution of AQP2
• C JAK-STAT pathway → STAT5 phosphorylation → nuclear AQP2 gene transcription within minutes
• D Gs → adenylyl cyclase → cAMP → PKA → phosphorylation of AQP2 vesicles → exocytosis to apical membrane ✓

Explanation

The V2 receptor is coupled to Gs; its activation stimulates adenylyl cyclase, elevates intracellular cAMP, and activates PKA. PKA phosphorylates AQP2 water channel proteins on serine 256 in cytoplasmic vesicles, triggering their exocytotic fusion with the apical membrane, dramatically increasing water permeability. This is the rapid (minutes) response; long-term ADH also up-regulates AQP2 gene expression. The Gq/IP3 pathway mediates V1 receptor effects (vasoconstriction). JAK-STAT is not involved in this rapid trafficking response.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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