MOLECULAR-CLONING AND EXPRESSION OF RAT V1A AND V2 ARGININE-VASOPRESSIN RECEPTORS

Vasopressin, one of the first characterized neuropeptides, has a wide spectrum of biological action, acting on distinct tissues. Indeed, it is involved in water retention, glucose metabolism, blood pressure and its implication in the CNS has also been described. This diversity of effects on mammalian tissues is mediated by distinct G protein-couple d receptors, acting via distinct second messenger pathways. This recep tor family has been subtyped by pharmacological studies, as V1a recept or whose action is mediated by intracellular calcium mobilization, and V2 receptor which is linked to adenylyl cyclase. Since so many essent ial functions were ensured by vasopressin, molecular characterization of its receptors became soon a great challenge. This prompted us to is olate the cDNA of AVP V1a receptor as the first member of this family, by expression cloning. Intracellular calcium mobilization was therefo re assayed after rat liver mRNA injection into Xenopus oocytes. A sing le clone, encoding a functional AVP receptor corresponding to the V1a subtype was finally characterized as a G protein-coupled receptor. Fur thermore, we used homology cloning strategy in order to clone the AVP V2 subtype from a rat kidney cDNA library. A putative receptor clone w as finally characterized as the rat V2 receptor cDNA by binding and cA MP increase experiments, on transfected cells.