Molecular cloning of at\ 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 ATr receptors and AT2 binding sites (Chiu AT, et al, Biochem Biophys Res Commun 1989;165:196-203). AT2 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 A receptors we have isolated rat cDNA's and genes encoding two distinct but highly similar isoforms of ATt receptors, termed ATla and ATBb receptors. Two cDNA's encoding the vascular ATla 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 ATt receptor was isolated from a genomic library. This receptor, termed the ATlb receptor, is 95% identical in amino acid sequence and is pharmacologically indistinguishable from the ATla receptor. However, the tissue-specific expression pattern of the ATlb gene differs significantly from that for the ATla receptor. Am J Hypertens 1992;5:236S-242S.