AMPHIBIAN MYOCARDIAL ANGIOTENSIN-II RECEPTORS ARE DISTINCT FROM MAMMALIAN AT1 AND AT2 RECEPTOR SUBTYPES

High-affinity receptors for angiotensin 11 were identified on Xenopus laevis cardiac membranes and characterized by binding-inhibition studies with peptide and non-peptide All antagonists. Scatchard analysis of the binding data identified a high-affinity site with K(d1) = 1.6 nM and B(max1) = 3.7 pmol/mg protein and a low-affinity site with K(d2) = 22 nM and B(max2) = 9.5 pmol/mg protein. Treatment with dithiothreitol reduced the number of binding sites by > 70%. The rank order of potency for All analogs was (agent, IC50) [Sar1,Ile8]AII, 0.91 nM > AII, 2.0 nM > AI, 5.3 nM > [Sar1,Ala8]AII, 19 nM >> CGP42112A, 1.2-mu-M >>> DuP 753 almost-equal-to PD-123177, > 100-mu-M. The relative potencies of these compounds differ markedly from their activities on the two known mammalian AII receptor subtypes, AT1, and AT2. These results indicate that amphibian AII receptors are pharmacologically distinct from both the AT1, and AT2, receptors characterized in mammalian tissues.