Which of the following vasopressin receptors MOST likely mediates vasopressin antidiuretic action?
The vasopressin receptor family is unique among all classes of peptide receptors, since its members couple to different subsets of G proteins. Vasopressin binds to four distinct types of receptor subtypes V1a, V1b, V2 and the oxytocin receptor. The V2 receptors are located on the basolateral membrane of collecting duct cells. This receptor belongs to the seven-transmembrane domain, G-protein-coupled receptor superfamily. Stimulation of the V2 receptor by vasopressin leads to the activation of a G protein (Gs), resulting in the activation of adenylyl cyclase, the production of cAMP, and the stimulation of protein kinase A (PKA). PKA stimulates aquaporin 2, a water channel protein, which undergoes vesicular trafficking, inseing into the apical membrane of the duct cells, thereby increasing the water permeability of that membrane. At maximal ADH levels, less than 1% of the filtered water is excreted, with the minimum urine volume of 500 mL/day and osmolality of 1200 mosmol/L. Long term regulation by vasopressin involves the effects of cAMP on the cAMP-response elements in the 5'-flanking region of the AQP2 gene, which increases the abundance of aquaporin 2 protein in the target cells. The human V2 receptor gene, AVPR2, is located in chromosome region Xq28. The genetic form of nephrogenic diabetes insipidus is caused by mutations in the coding region of the V2 receptor gene. Note: AQP6 is a water channel protein that is localized exclusively in intracellular membranes in renal epithelia. Vasopressin has low affinity for oxytocin receptors. The oxytocin receptor is a typical class I G protein-coupled receptor, primarily stimulating phospholipase C beta activity. The V1a receptor mediates smooth muscle contraction (vasoconstriction in splanchnic, coronary, cerebral, peripheral, pulmonary, and intrahepatic vessels), platelet aggregation, hepatic glycogenolysis, and coagulation factor release by vasopressin. It is also proposed that brain V1a vasopressin receptors may mediate the effect of ADH on sho-term memory and learning, antipyresis, cardiovascular responsivity, and brain development. Ref: Reid I.A. (2012). Chapter 17. Vasoactive Peptides. In B.G. Katzung, S.B. Masters, A.J. Trevor (Eds), Basic & Clinical Pharmacology, 12e.
AQP6
Oxytocin receptor
V1a
V2