Endothelins: homeostatic and compensatory actions in the circulatory and endocrine systems.

Abstract

I. Introduction ENDOTHELIN (ET) is a potent vasoconstrictive peptide which was originally isolated from the conditioned medium of cultured endothelial cells (1). It comprises 21 aminoacid residues, including four cysteine residues that form two disulfide bonds (see Fig. 1). ET elicits a sustained pressor response when administrated intravenously, which suggests its importance in blood pressure maintenance and generation of vasospasm. Accordingly, many investigators have been interested in this peptide. Analysis of ET genes revealed the existence of three distinct ET genes that encode different mature ET sequences, designated endothelin-1 (ET-1), ET-2, and ET-3 (Fig. 1) (2). Two and six amino acid residues of ET-1 are replaced in ET-2 and ET-3, respectively. There are no species differences among isoforms of human, porcine, rat, bovine, or dog. Interestingly, the structure of snake venom sarafotoxins are very similar to those of ETs. In endothelial cells, ET-1 is predominant, but ET-2 and ET-3 are not dete...