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The actions of vasopressin are mediated by stimulation of tissue-specific G protein-coupled receptors (GPCRs) called vasopressin receptors that are classified into the V1 (V1A), V2, and V3 (V1B) receptor subtypes. These three subtypes differ in localization, function and signal transduction mechanisms.
| vasoconstriction, myocardial hypertrophy, platelet aggregation, glycogenolysis, uterine contraction |
| releases ACTH, prolactin, endorphins |
| insertion of AQP-2 water channels into apical membrane, induction of AQP-2 synthesis, releases von Willebrand factor and factor VIII, vasodilation |
V1R is present on platelets, which upon stimulation induces an increase in intracellular calcium, facilitating thrombosis. Studies have indicated that due to polymorphism of platelet V1R there is significant heterogeneity in the aggregation response of normal human platelets to vasopressin.
V1Rs are found in kidney, where they occur in high density on medullary interstitial cells, vasa recta, and epithelial cells of the collecting duct. Vasopressin acts on medullary vasculature through V1R to reduce blood flow to inner medulla without affecting blood flow to outer medulla. V1Rs on the luminal membrane of the collecting duct limit the antidiuretic action of vasopressin. Additionally, vasopressin selectively contracts efferent arterioles probably through the V1R, but not the afferent arteriole.
The well known antidiuretic effect of vasopressin occurs via activation of V2R. Vasopressin regulates water excretion from the kidney by increasing the osmotic water permeability of the renal collecting duct – an effect that is explained by coupling of the V2R with the Gs signaling pathway, which activates cAMP. The V2R continues to activate Gs after being internalized by β-arrestin rather than being desensitized. This internalized Gs signaling by V2R is explained by the receptors ability to form "mega-complexes" consisting of a single V2R, β-arrestin, and heterotrimeric Gs. The increased intracellular cAMP in the kidney in turn triggers fusion of aquaporin-2-bearing vesicles with the apical plasma membrane of the collecting duct principal cells, increasing water reabsorption.
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Normally, when osmolality falls below its set point, plasma vasopressin levels become undetectable, and an aquaresis results. In SIADH, vasopressin release is not fully suppressed, despite hypotonicity. In cirrhosis and CHF, impaired delivery of solute to the diluting sites or diminished glomerular filtration rate causes impairment of maximal water-excretory capacity, resulting in persistence of vasopressin release leading to water retention.
Vasopressin receptor antagonists include the new class of "vaptan drugs" such as conivaptan, tolvaptan, mozavaptan, lixivaptan, satavaptan etc.
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