Endothelin peptide family

Endothelin. The endothelin (ET) peptide family (50) comprises thiee peptides ET-1 (133), ET-2 (134), and ET-3 (135). ET-1, the most abundant, is a 21-amino acid peptide. A 203-amino acid peptide piecuisoi, piepioET, is cleaved after translation by endopeptidases to form a 38-amino acid proET which is converted to active ET by a putative endothelin-converting enzyme (ECE). ET-3 differs from ET-1 and ET-2 by sis amino acids. 

Endothelins comprise a family of three vasoactive isopeptides of 21 amino acids that have an essential role in the regulation of the vascular and bronchiolar tone and the control of natriuresis in the kidney. Endothelin peptides are also involved in nociception and have a critical role in the progression of prostate and ovarian cancer. 

Endothelins are a family of vasoactive peptides secreted by endothelial cells. The three major endothelin peptides are all composed of 21 amino acids. Endothelins are the most potent vasoconstrictors known. Contraction of vascular smooth muscle in response to endothelin is associated with an increase in intracellular calcium. Increases in endothelin levels have been reported in patients with vasospastic, hypoxic, and ischemic diseases. The two identified isoforms of endothelin receptors have differing affinity for the three endothelin peptides. Selective and nonselective endothelin receptor antagonists are in development for potential use in the treatment of hypertension and other disorders associated with increased vascular resistance. 

Simonson MS, Dunn MJ. Cellular signaling hy peptides of the endothelin gene family. FASEB J 1990 4 2989-3000. 

Of this family of peptides containing two intramolecular disulfide bonds the most studied in terms of oxidative refolding are a-conotoxins with two adjacent cysteine residues, i.e. with m = 0, the bee venom toxins, for example apamin and mast cell degranulating peptide, and snake venom toxins, exemplified by sarafotoxins, and endothelins, mammalian peptide hormones with the characteristic Cys-(Xaa)rCys/Cys-(Xaa)3-Cys motif (Scheme 2). With m = 0 or 1 all these peptides are expected to show a weak tendency to form the isomer 3 with a disulfide bond between two proximal cysteine residues. This was fully confirmed by oxidative refolding experiments. 

The endothelium is the source of a variety of substances with vasodilator (PGI2 and nitric oxide) and vasoconstrictor activities. The latter include the endothelin family, potent vasoconstrictor peptides that were first isolated from aortic endothelial cells. 

Fig. 8. (a) Primary structure of the cyclic endothelin antagonist BE18257B and (b) a family of 36 NMR structures which demonstrates the well-defined nature of the cyclic peptide backbone. (Reprinted with permission from Coles et a/.148 Copyright (1993) American Chemical Society.)... 

Endothehns constitute a family of peptides (Hart and Hart, 1992). They are very potent endogenous vasoconstrictors and vasopressors and are secreted by various cells and tissues in the human body. Of the three isoforms, endothe-hn-1 (ET-1) is one of the most potent contractors of vascular smooth muscles (Miller et al, 1993). Endothelins have very similar structures and biological properties to sarafotoxins (Kloog and Sokolovsky, 1989), and the toxic peptides are obtained from the venom of mole vipers (Atractaspidae). 

The endothelin family consists of three members, ENDO-THELIN-l ENDOTHELIN-2 and ENDOTHELIN-3. All three peptides contain 21 amino acids, but vary in amino acid composition. The three peptides produce vasoconstrictor and pressor responses in various parts of the body. However, the quantitative profiles of the pharmacological activities are considerably different among the three isopeptides. 

The endothelins belong to a family of potent vasoconstrictor peptides that were originally isolated from the supernatant of cultured aortic endothelial cells. Endothehns bear striking structural similarities to the sarafotoxins, which are potent cardiotoxic peptides isolated from the venom of the burrowing asp Atractaspis engadensis. Four endothelins and four sarafotoxin isopeptides, having different receptor sub-types, have been identified (see also Figure 44). 

Sarafotoxins (SRTX), CSCKDMTDKE CL NFCHQDVTIw (SRTX-a) (disulfide bonds C -C /C -C ), a family of vasoactive peptides initially isolated from the venom of Atractaspis engaddensis. The highly toxic peptides (SRTX-a, -h, -c, -e) are structurally and functionally related to endothelins (ET). Each of the members of the ET-SRTX family contains four Cys, and about 60-70% of their 21 amino acid residues are identical. The SRTX cause strong vasoconstriction of coronary arteries. Death after intoxication with SRTX peptides is the result of cardiac ischemia or infarction. Sarafotoxins and sarafotoxin-like peptides are produced by various snake... 

Endothelins (ET-1 to ET-3 and others) are a family of 21 amino acid residue peptides containing two conformationally constraining disulfide bonds. ... 

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