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Vasopressin Receptors

*The cellular effects of vasopressin (ADH) are mediated mainly by interactions of the hormone with the three types of receptors, V1a, V1b, and V2.

*The V1a receptor is the most widespread subtype of Vasopressin receptor; it is found in vascular smooth muscle, the adrenal gland, myometrium, the bladder, adipocytes, hepatocytes, platelets, renal medullary interstitial cells, vasa recta in the renal microcirculation, epithelial cells in the renal cortical collecting-duct, spleen, testis, and many CNS structures.

*V1b receptors have a more limited distribution and are found in the anterior pituitary, several brain regions, the pancreas, and the adrenal medulla.

*V2 receptors are located predominantly in principal cells of the renal collecting-duct system but also are present on epithelial cells in the thick ascending limb and on vascular endothelial cells.

*Although originally defined by pharmacological criteria, vasopressin receptors now are defined by their primary amino acid sequences.

*The cloned vasopressin receptors are typical heptahelical G protein–coupled receptors.

*Manning and coworkers (1999) have synthesized novel hypotensive vasopressin peptide agonists that do not interact with V1a, V1b, or V2 receptors and may stimulate a putative vasopressin vasodilatory receptor. Finally, two additional putative receptors for vasopressin have been cloned.

*A vasopressin-activated Ca2+-mobilizing receptor with one transmembrane domain binds vasopressin and increases intracellular Ca2+. A dual angiotensin II–vasopressin heptahelical receptor activates adenylyl cyclase in response to both angiotensin II and vasopressin. The physiological roles of these putative vasopressin receptors are unclear.

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