CLONING AND CHARACTERIZATION OF A NOVEL ENDOTHELIN RECEPTOR FROM XENOPUS HEART

Endothelin (ET) receptors display subtype heterogeneity and so far thr ee subtypes of ET receptors, namely ET(A), ET(B), and ET(C), have been identified, cloned, sequenced, and characterized. Based on the bindin g profile of ET and related peptides, a novel ET receptor (ET(AX)) was identified in the follicular membranes of Xenopus laevis oocytes (Kum ar, C. S., Nuthulaganti, P., Pullen, M., and Nambi, P. (1993). Mol. Ph armacol. 44, 153-157). Here we report the cloning and characterization of this ET(AX) subtype from X. Laevis heart. A cDNA was isolated that encodes a protein of 415 amino acids that shares 74, 60, and 51% iden tities with human ET(A), human ET(B), and Xenopus ET(C) receptors, res pectively. Competition binding studies of the cloned receptor expresse d in COS cells using ET-related peptides suggested that this receptor is pharmacologically identical to that expressed in Xenopus oocyte fol licular, heart, and lung membranes. Phosphoinositide turnover and oocy te electrophysiological studies indicated that the cloned receptor is functionally coupled to a second messenger system.