CHARACTERIZATION OF A FUNCTIONAL ANGIOTENSIN-II RECEPTOR IN XENOPUS-LAEVIS HEART

High-affinity(104 +/- 18 pmol/l) and high-density (204 +/- 25 fmol/mg) angiotensin II (AII) binding sites have been identified in Xenopus la evis heart membranes. Competition binding of [I-125]Sar(1),Ile(8) angi otensin (SIA) to these receptors by peptide analogs selective for the mammalian AII receptor subtypes AT(1) and AT(2) suggested that the amp hibian AII binding sites were more closely related to the AT(1) recept or subtype. Also in common with AT(1) receptors, dithiothreitol and GT P gamma S inhibited [I-125]SIA binding to Xenopus heart receptors, exh ibiting IC50 values of 600 and 0.95 mu mol/l, respectively. In additio n, Xenopus oocytes injected with Xenopus heart mRNA were capable of mo bilizing calcium when exposed to AII, demonstrating that Xenopus AII r eceptors are functionally linked to a second-messenger system similar to that coupled to mammalian AT(1) receptors. However, in contrast to both AT(1) and AT(2) receptor subtypes, nonpeptide antagonists DUP 753 and SK&F 108566 (AT(1) receptor selective) and PD123319 (AT(2) select ive) did not bind the Xenopus AII receptors, thus establishing that th e amphibian receptors were pharmacologically unique. Together, these r esults demonstrate that Xenopus heart AII receptors are functionally s imilar to mammalian AT(1) receptors but are pharmacologically distinct from both AT(1) and AT(2) receptors.