Site of Action of Antidiuretic Hormone
The site of action of antidiuretic hormone (ADH) is the collecting ducts of the kidney. 1, 2, 3
Mechanism of Action
ADH (also known as vasopressin) acts specifically on the collecting ducts through the following mechanism:
- Binds to vasopressin V2 receptors (V2R) expressed on the basolateral membrane of collecting duct cells 1
- Initiates a signaling cascade involving:
- Results in the exocytic insertion of aquaporin-2 (AQP2) water channels into the apical membrane of collecting duct cells 1, 4
- Water then flows from the tubule lumen to the hypertonic medullary interstitium through:
Evidence Supporting Collecting Ducts as the Primary Site
The collecting ducts are definitively established as the primary site of ADH action based on several lines of evidence:
The FDA drug label for desmopressin (synthetic ADH analog) explicitly states: "The antidiuretic effects of desmopressin acetate are mediated by stimulation of vasopressin 2 (V2) receptors, thereby increasing water re-absorption in the kidney" 3
Consensus statements from the European Reference Network on Rare Kidney Diseases specifically illustrate the mechanism of "vasopressin-regulated water reabsorption in the distal collecting duct" 1
Clinical guidelines note that ADH's action enables "the formation of concentrated urine" through its effects on collecting duct water permeability 1, 2
Clinical Implications
Understanding ADH's site of action is crucial for managing several clinical conditions:
In nephrogenic diabetes insipidus (NDI), there is resistance to ADH at the collecting ducts, leading to inability to concentrate urine despite normal ADH secretion 1
In syndrome of inappropriate ADH secretion (SIADH), excessive ADH causes increased water reabsorption at the collecting ducts, leading to hyponatremia 2
Therapeutic agents like tolvaptan work by antagonizing vasopressin receptors in the collecting ducts, making them useful for treating conditions with excess ADH activity 2
Physiological Regulation
The collecting duct response to ADH is dynamically regulated:
- When ADH is present: AQP2 water channels are inserted into the apical membrane, increasing water permeability
- When ADH is withdrawn: AQP2 channels are retrieved by endocytosis, decreasing water permeability 4, 5
- Flow rate through the collecting duct can affect the degree of osmotic equilibration between urine and renal papilla, even in the presence of maximal ADH 6
Therefore, based on the most current and authoritative evidence, the correct answer is (a) collecting ducts.