Lack of biological activity of preproendothelin [110-130] in several endothelin assays

• Published in: Life sciences (1973) Vol. 47; no. 23; p. 2097
• Main Authors: Cade, C, Lumma, Jr, W C, Mohan, R, Rubanyi, G M, Parker-Botelho, L H
• Format: Journal Article
• Language: English
• Published: Netherlands 1990
• Subjects: Amino Acid Sequence; Animals; Binding, Competitive; Cell Membrane; Cricetinae; Disulfides; Dogs; Endothelin-1; Endothelins - chemical synthesis; Endothelins - physiology; Humans; Molecular Sequence Data; Myocardium - cytology; Protein Precursors - chemical synthesis; Protein Precursors - physiology; Radioimmunoassay; Viper Venoms - pharmacology
• ISSN: 0024-3205
• DOI: 10.1016/0024-3205(90)90308-E

A 21 amino acid peptide containing the prepropendothelin sequence from amino acids 110 to 130 and two intrachain disulfide bonds was synthesized and tested for biological activity in the following endothelin assays: 1.) a competition binding assay using [125I]ET-1 and dog heart membranes, 2.) three RIA's using 125I-ET-1, -2 and -3 and the respective anti-ET rabbit antisera; and 3.) a contractile activity bioassay using hamster aortic rings. The synthetic peptide which has been referred to as the "endothelin-like" peptide occurs 36 amino acids C-terminal to endothelin in the prepro-protein sequence. It contains only 40% sequence homology to the three endothelin isoforms, but has the same sequence and cyclization pattern of cysteines at positions 1, 3, 11 and 15. Despite the overall similarity in secondary structure to the three isoforms of endothelin and sarafotoxin S6b, preproendothelin [110-130] had no activity in any of the assays when tested at concentrations of 10(-10)M to 10(-5)M.