Vascular Biology of the Endothelin System

摘要: The identification and characterisation of endothelin in 1988 [1] followed the discovery that an endothelium-derived relaxing factor (EDRF) mediates vascular relaxation to acetylcholine [2] subsequent this as nitric oxide [3]. An additional important stimulus was recognition endothelial cells culture generate release a polypeptide vasoconstrictor into bathing medium [4–6]. In tour de force for cardiovascular biology, Yanagisawa, Masaki colleagues identified characterised 21 amino acid peptide most potent constrictor then known. Subsequent studies have shown isolated from (now known endothelin-1) is one family isopeptides (Fig.1), each which contains two intra-chain disulphide bridges linking paired cysteine residues all are formed through same processing pathway (Fig. 2). Their respective precursor peptides share high sequence homology but encoded by distinct genes [7]. It also clear [8] remarkable structural similarity sarafotoxins, venom Israeli burrowing asp, Atractaspis engaddensis 1). sarafotoxins endothelins receptor binding sites, signalling pathways pharmacological actions. Indeed, isoforms sarafotoxin proved valuable tools characterising receptors [9].