Correct Answer: B. 2
ADH (antidiuretic hormone/vasopressin) exerts its water-reabsorbing effect in the collecting duct of the nephron by binding to V2 receptors on the basolateral membrane of principal cells. This G-protein coupled receptor activation triggers a cAMP-dependent cascade that phosphorylates and inserts aquaporin-2 (AQP2) water channels into the apical membrane. AQP2 is the rate-limiting step for water reabsorption in the collecting duct—without it, water cannot cross the apical membrane despite the osmotic gradient. The basolateral membrane also expresses AQP3 and AQP4 for water exit, but AQP2 is the ADH-regulated channel and the physiologically critical one. This mechanism is fundamental to urine concentration and osmolarity regulation in the distal nephron. In clinical practice, nephrogenic diabetes insipidus (NDI) often involves AQP2 mutations or dysfunction, preventing ADH-mediated water reabsorption despite normal hormone levels—a key distinction from central DI seen in Indian patients with pituitary pathology.
Why the other options are wrong
A. 4 — Aquaporin-4 (AQP4) is expressed in astrocytes and the blood–brain barrier, not in the collecting duct principal cells. While AQP4 is involved in cerebral edema and osmolarity regulation in the CNS, it plays no role in ADH-mediated renal water reabsorption. This is a distractor that tests whether students confuse aquaporin distribution across tissues. C. 1 — Aquaporin-1 (AQP1) is found in the proximal convoluted tubule and descending limb of the loop of Henle, where it permits constitutive (ADH-independent) water reabsorption. AQP1 is not regulated by ADH and is not involved in the collecting duct's osmolarity-dependent water handling. NBE uses this to trap students who know AQP1 is important in the nephron but forget its location and function. D. 3 — Aquaporin-3 (AQP3) is expressed on the basolateral membrane of collecting duct principal cells and serves as the exit route for water reabsorbed via AQP2. However, AQP3 is constitutively present and not regulated by ADH; it is not the ADH-responsive channel. Confusing basolateral AQP3 with apical AQP2 is a common error among students learning collecting duct physiology.
High-Yield Facts
- Aquaporin-2 (AQP2) is the ADH-regulated water channel in the collecting duct apical membrane, inserted via cAMP-dependent phosphorylation.
- AQP1 is constitutive in proximal tubule and loop of Henle; AQP3 and AQP4 are basolateral exit channels—neither is ADH-regulated.
- Nephrogenic DI results from AQP2 mutations or V2 receptor defects, causing polyuria despite high ADH levels; central DI is ADH deficiency.
- V2 receptor antagonists (vaptans) block ADH signaling and are used in SIADH; they do not directly affect AQP2 insertion but prevent its activation.
- Urine osmolarity in the collecting duct depends on AQP2-mediated water reabsorption; loss of AQP2 function results in dilute urine regardless of ADH concentration.
Mnemonics
AQP in the Nephron (PLLCD rule) Proximal = AQP1 (constitutive); Loop = AQP1 (constitutive); Loop exit = AQP1; Collecting duct = AQP2 (ADH-regulated apical) + AQP3/4 (basolateral); Distal = minimal water permeability. Remember: only AQP2 in collecting duct is ADH-sensitive. ADH → AQP2 → Water ADH binds V2 → cAMP ↑ → AQP2 phosphorylated → AQP2 inserted into apical membrane → water reabsorbed. This linear cascade is the testable mechanism in every NEET PG exam.
NBE Trap
NBE pairs aquaporins with the nephron to lure students into naming AQP1 (proximal tubule) or AQP3 (basolateral exit) instead of recognizing that only AQP2 is ADH-responsive. The trap exploits confusion between "aquaporin in the collecting duct" and "ADH-regulated aquaporin."
Clinical Pearl
In Indian patients presenting with polyuria and polydipsia, distinguishing central DI (ADH deficiency, responds to desmopressin) from nephrogenic DI (AQP2/V2 receptor defect, does not respond) is critical—the water deprivation test followed by desmopressin challenge is the gold standard. Recognizing AQP2 dysfunction helps clinicians understand why some NDI patients fail to concentrate urine despite high endogenous ADH.
_Reference: Guyton & Hall Textbook of Medical Physiology Ch. 28 (Urine Formation); Harrison Principles of Internal Medicine Ch. 276 (Disorders of Sodium and Water Homeostasis)_