ISOLATION AND CHARACTERIZATION OF 2 ALTERNATIVELY SPLICED COMPLEMENTARY DNAS ENCODING A XENOPUS-LAEVIS ANGIOTENSIN-II RECEPTOR

We have isolated two cDNAs of 1.7 and 3.0 kb, produced by alternative splicing, that encode an angiotensin II (AII) receptor from a Xenopus laevis heart cDNA library. The two clones had identical coding regions with each other and were found to belong to the G protein-coupled rec eptor superfamily like the mammalian type 1 AII receptors (AT(1)); the ir amino acid sequence was 68.7% homologous with the human AT(1) recep tor sequence. However, there was a 1.3 kb insertion at the S'-untransl ated region of the longer clone. The insertion contained 9 repeats of an ATTTA motif, suggesting that the two mRNAs undergo distinct post-tr anscriptional regulation by virtue of a difference in their stability. Although the Xenopus receptor exhibited distinct specificities for AI I receptor antagonists compared with mammalian AII receptors, several common characteristics, including the effect of dithiothreitol and gua nosine 5'-O-(3-thiotriphosphate), demonstrated that the cloned recepto r is a counterpart of the mammalian AT(1) receptor. Moreover, the clon ed receptor was expressed most abundantly in the Xenopus heart, which is inconsistent with the tissue distribution of mammalian AII receptor s. This indicated that the Xenopus heart, unlike that of mammals, play s a major role in the AII-dependent regulation of blood pressure and e xtracellular fluid volume.