MOLECULAR-CLONING OF AT1 ANGIOTENSIN RECEPTORS

Angiotensin II is the principal effector molecule of the renin-angiotensin system. Its effects are mediated by cell surface proteins termed AT receptors On the basis of radioligand binding studies, these have been pharmacologically subdivided into two classes, termed AT1 receptors and AT2 binding site (Chiu AT, et al, Biochem Biophys Res Commun 1989;165:196 - 203). AT1 receptors appear to mediate the major cardiovascular effects of angiotensin II, whereas no known physiological properties appear to be coupled to AT2 binding sites (Wong PC, et al, J Pharmacol Exp Ther 1990;255:584 - 592). To gain further insight into the function of AT1 receptors we have isolated rat cDNA's and genes encoding two distinct but highly similar isoforms of AT1 receptors, termed AT1a and AT1b receptors. Two cDNA's encoding the vascular AT1a receptor were isolated by an expression cloning strategy from a cDNA library prepared from vascular smooth muscle cells. The properties of the clones isolated by this approach are consistent with known pharmacological, biochemical signaling, and tissue distribution properties of AT1 receptors. Using this cDNA as a probe, a second isoform of rat AT1 receptor was isolated from a genomic library. This receptor, termed the AT1b receptor, is 95% identical in amino acid sequence and is pharmacologically indistinguishable from the AT1a receptor. However, the tissue-specific expression pattern of the AT1b gene differs significantly from that for the AT1a receptor.