## ADH Mechanism of Action on Collecting Duct **Key Point:** ADH (vasopressin) acts on V2 receptors on the basolateral membrane of collecting duct principal cells, triggering a cAMP-dependent cascade that results in translocation of aquaporin-2 (AQP2) water channel-containing vesicles to the apical membrane. ### Step-by-Step Mechanism 1. ADH binds to V2 receptor → activation of adenylyl cyclase 2. Increased intracellular cAMP → activation of protein kinase A (PKA) 3. PKA phosphorylates aquaporin-2 channels in intracellular vesicles 4. Phosphorylated AQP2 channels translocate to apical membrane via exocytosis 5. Water channels now present on apical surface → osmotic water reabsorption 6. Water exits via basolateral aquaporin-3 and aquaporin-4 channels (constitutive) **High-Yield:** The **reversibility** of this mechanism is critical: when ADH levels drop, AQP2 channels are rapidly internalized by endocytosis, reducing water permeability within minutes. This allows rapid adjustment of urine osmolality. **Clinical Pearl:** Nephrogenic diabetes insipidus (NDI) results from loss-of-function mutations in AQP2 or V2 receptor genes, preventing this water channel insertion despite normal/elevated ADH levels. **Mnemonic:** **CAMP** — **C**ollecting duct, **A**quaporin-2, **M**embrane insertion, **P**rotein kinase A phosphorylation. ### Why This Matters This mechanism explains why ADH is the **final regulator of water balance** — it acts distal to the proximal tubule and loop of Henle, fine-tuning the osmolality of final urine from 50 mOsm/kg (no ADH) to 1200 mOsm/kg (maximal ADH).
Sign up free to access AI-powered MCQ practice with detailed explanations and adaptive learning.