Antidiuretic hormone (vasopressin) - physiology and site of action
Core concept
- Made in the supraoptic nucleus (mainly) and paraventricular nucleus -> travels down axons -> stored and released from the posterior pituitary
- Posterior pituitary is neural tissue, not glandular - a stalk lesion causes DI, and the gland itself makes nothing
Receptors - three, and each is a drug target
| Coupling | Site | Effect | |
|---|---|---|---|
| V2 | Gs -> cAMP -> PKA | Basolateral membrane, collecting duct principal cell | AQP2 inserted into apical membrane -> water reabsorption. Also inc UT-A1 and NKCC2 -> maintains medullary gradient |
| V1a | Gq | Vascular smooth muscle, platelets, hepatocyte | Vasoconstriction |
| V1b (V3) | Gq | Anterior pituitary corticotroph | Potentiates CRH-driven ACTH release |
- Two independent triggers
- Osmotic - hypothalamic osmoreceptors, threshold ~280-285 mOsm/kg, responds to a 1% change
- Volume (baroreceptor) - carotid sinus and aortic arch; needs a ~8-10% fall in volume, but then overrides the osmostat entirely
- -> the hyponatraemia of hypovolaemia, heart failure and cirrhosis
3 more sections, plus exam facts
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