A patient with central diabetes insipidus receives a low dose of exogenous ADH. The primary renal tubular location where ADH exerts its major antidiuretic effect, and the intracellular mediator involved, are:

• A Proximal tubule; cAMP-mediated insertion of AQP1
• B Thick ascending limb of Henle; cAMP-mediated activation of NKCC2 cotransporter
• C Cortical collecting duct and medullary collecting duct; cAMP-mediated phosphorylation and apical insertion of AQP2 water channels ✓
• D Descending thin limb; direct channel activation without second messenger

Explanation

ADH (vasopressin) binds V2 receptors on principal cells of the cortical and medullary collecting duct. V2 receptor coupling to Gs protein activates adenylyl cyclase, increasing intracellular cAMP, which activates PKA. PKA phosphorylates AQP2 water channels stored in subapical vesicles, promoting their fusion with the apical membrane—increasing water permeability dramatically. The basolateral AQP3 and AQP4 channels are constitutively expressed. AQP1 in the proximal tubule and descending thin limb is constitutively active and not regulated by ADH. NKCC2 in the thick ascending limb is important for medullary gradient generation but is not the antidiuretic target of ADH.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.