Figure 135

Vasopressin receptors. Vasopressin exerts its cellular actions through two major receptors. Activation of V1 receptors leads to vascular smooth muscle constriction and increases peripheral resistance. Vasopressin stimulates inositol 1,4,5-triphosphate and calcium ion (Ca2+) mobilization from cytosolic stores and also increases Ca2+ entry from extracellular stores as shown in Figure 1-10. The vaso-constrictive action of vasopressin helps increase total peripheral resistance and reduces medullary blood flow, which enhances the concentrating ability of the kidney. V2 receptors are located primarily on the basolateral side of the principal cells in the collecting duct segment. Vasopressin activates heterotrimeric G proteins that activate adenylate cyclase, thus increasing cyclic AMP levels. Cyclic AMP (cAMP) activates protein kinase A, which increases the density of water channels in the luminal membrane. Water channels (aqua-porin proteins) reside in subapical vesicles and on activation fuse with the apical membrane. Thus, vasopressin markedly increases the water permeability of the collecting duct and allows conservation of fluid and excretion of a concentrated urine. An intact vasopressin system is essential for the normal regulation of urine concentration by the kidney that, in turn, is the major mechanism for coupling the solute to solvent ratio (osmolality) of the extracellular fluid. As discussed in Figure 1-4, this tight coupling allows the confluence of homeostatic mechanisms regulating sodium balance with those regulating extracellular fluid volume. Ga and G—proteins; PPi— inorganic pyrophosphate. (Adapted from Vari and Navar [4].)

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