Expansion
It inserts aquaporin-2 channels into the collecting duct
Expansion
Antidiuretic hormone acts on V2 receptors on the basolateral membrane of the collecting duct principal cell:
- V2 receptor activates adenylate cyclase, raising cyclic AMP
- Aquaporin-2 vesicles fuse with the apical membrane
- Water moves out of the tubule down the osmotic gradient created by the countercurrent multiplier
- Aquaporins 3 and 4 on the basolateral side allow water to leave the cell
It also increases urea permeability of the inner medullary collecting duct, which reinforces the gradient, and stimulates NKCC2 activity.
Urine osmolality can therefore range from 50 mOsm/kg (maximal dilution, no hormone) to 1200 mOsm/kg (maximal concentration).
Disorders map onto the pathway:
- Central diabetes insipidus: no hormone; responds to desmopressin
- Nephrogenic diabetes insipidus: receptor or aquaporin failure, or lithium toxicity; does not respond
- SIADH: excess hormone, causing water retention and dilutional hyponatraemia