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 laevis heart membranes. Competition binding of [I-125]Sar(1),Ile(8) angiotensin (SIA) to these receptors by peptide analogs selective for the mammalian AII receptor subtypes AT(1) and AT(2) suggested that the amphibian AII binding sites were more closely related to the AT(1) receptor subtype. Also in common with AT(1) receptors, dithiothreitol and GTP gamma S inhibited [I-125]SIA binding to Xenopus heart receptors, exhibiting IC50 values of 600 and 0.95 mu mol/l, respectively. In addition, Xenopus oocytes injected with Xenopus heart mRNA were capable of mobilizing calcium when exposed to AII, demonstrating that Xenopus AII receptors 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) selective) did not bind the Xenopus AII receptors, thus establishing that the amphibian receptors were pharmacologically unique. Together, these results demonstrate that Xenopus heart AII receptors are functionally similar to mammalian AT(1) receptors but are pharmacologically distinct from both AT(1) and AT(2) receptors.