Kumar C, Mwangi V, Nuthulaganti P, Wu H L, Pullen M, Brun K, Aiyar H, Morris R A, Naughton R, Nambi P
Department of Molecular Genetics, SmithKline Beecham Pharmaceuticals, King of Prussia, Pennsylvania 19406-0939.
J Biol Chem. 1994 May 6;269(18):13414-20.
Endothelin (ET) receptors display subtype heterogeneity and so far three subtypes of ET receptors, namely ETA, ETB, and ETC, have been identified, cloned, sequenced, and characterized. Based on the binding profile of ET and related peptides, a novel ET receptor (ETAX) was identified in the follicular membranes of Xenopus laevis oocytes (Kumar, C. S., Nuthulaganti, P., Pullen, M., and Nambi, P. (1993). Mol. Pharmacol. 44, 153-157). Here we report the cloning and characterization of this ETAX subtype from X. laevis heart. A cDNA was isolated that encodes a protein of 415 amino acids that shares 74, 60, and 51% identities with human ETA, human ETB, and Xenopus ETC receptors, respectively. Competition binding studies of the cloned receptor expressed in COS cells using ET-related peptides suggested that this receptor is pharmacologically identical to that expressed in Xenopus oocyte follicular, heart, and lung membranes. Phosphoinositide turnover and oocyte electrophysiological studies indicated that the cloned receptor is functionally coupled to a second messenger system.
内皮素（ET）受体表现出亚型异质性，到目前为止，已鉴定、克隆、测序并表征了三种ET受体亚型，即ETA、ETB和ETC。基于ET及相关肽的结合特征，在非洲爪蟾卵母细胞的滤泡膜中鉴定出一种新型ET受体（ETAX）（Kumar, C. S., Nuthulaganti, P., Pullen, M., and Nambi, P. (1993). Mol. Pharmacol. 44, 153 - 157）。在此，我们报告从非洲爪蟾心脏克隆并表征这种ETAX亚型。分离出一个cDNA，其编码一种415个氨基酸的蛋白质，该蛋白质与人类ETA、人类ETB和非洲爪蟾ETC受体的同源性分别为74%、60%和51%。使用ET相关肽对在COS细胞中表达的克隆受体进行的竞争结合研究表明，该受体在药理学上与在非洲爪蟾卵母细胞滤泡、心脏和肺膜中表达的受体相同。磷酸肌醇代谢和卵母细胞电生理研究表明，克隆的受体在功能上与第二信使系统偶联。
