ANGIOTENSIN-II RECEPTORS - CLONING AND EXPRESSION

To identify the mechanisms of action of isoforms angiotensin II receptors (AT(1A), AT(1B), and AT(2)) and to overcome the difficulties encountered in attempts to purify the receptors, we have expression-cloned their cDNAs from bovine and rat sources and isolated human cDNA and rat and human genomic DNA. The AT(1A) and AT(1B) cDNAS were found to encode respective receptor proteins with 359 amino acid residues, whereas, AT(2) encodes a 363 amino acid residue receptor protein. Both AT(1) and AT(2) were found to conform with the seven transmembrane receptor structural motif, but showed only 32% amino acid residue identity to each other. The AT(1) receptor was shown to be coupled to, at least, three different G proteins activating phospholipase C, inhibiting adenylyl cyclase and opening an L-type Ca2+-channel, whereas, AT(2) was found to inhibit a phosphotyrosine phosphatase activity without affecting guanylyl cyclase by a pertussis-toxin-sensitive, presumably G-protein-mediated mechanism.