Molecular cloning, sequencing and functional expression of an amphibian angiotensin II receptor

Xenopus laevis and mammalian angiotensin AT1 receptors couple to the phospholipase C signal transduction pathway. However, amphibian AII receptors (xAT), unlike mammalian AT1 receptors, do not recognize the non-peptide antagonist Dup 753. To investigate the basis of this distinction, we have isolated a 3.0 kb Xenopus myocardial xAT cDNA that encodes a 41,039 MW protein containing 362 amino acids. The xAT receptor has 60% amino acid identity and 65% nucleotide homology with the coding regions of known mammalian AT1 receptors. xAT receptors expressed in Xenopus oocytes mediate AII-induced Ca2+ mobilization and are pharmacologically distinct from mammalian AT1 receptors. xAT transcripts are present in Xenopus lung, liver, kidney, spleen, and heart, but not in adrenal, intestine, and smooth muscle. Comparative analysis of xAT and AT1 receptors should facilitate elucidation of the structural basis of their binding and activation properties.