A family of peptides acting locally as autacoid or paracrine hormones. Three isoforms of the 21 amino acid peptide have been identified: ET-1, ET-2 andET-3. They are produced by a variety of cells, including endothelial and epithelial cells, macrophages and fibroblasts. Endothelins are characterised by two intra-chain disulphide rings, leading to a hairpin loop configuration, along with six conserved amino acid residues at the C terminus.

Endothelins are synthesised by the proteolysis of large pre-proendothelins, e which are cleaved to big endothelins, and then processed to the mature peptide by endothelin-converting enzyme. s

Endothelins induce dose-dependent contraction in vascular smooth muscle, S'

ET-1 being the most potent known endogenous vasoconstrictor. Two high affinity g endothelin receptors have been recognised, ETA and ETB. They have been |

characterised as seven transmembrane domain G-protein receptors coupled to h.

phospholipase C. The ETA receptor is the predominant type of receptor. g

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