Endothelin peptides

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Abstract
Application of gene knockout techniques to endothelin research has led to the revelation of unexpected and interesting roles for endothelin isopeptides and their receptors. Homozygous mice with null endothelin-1 and ETA receptors presented with craniofacial and cardiovascular malformations, indicating that these receptors are essential for the development of the first branchial arch derived from the neural crest. Homozygous mice with null endothelin-3 and ETB receptors presented with megacolon (Hirschsprung's disease) associated with spotted colour coats, indicating that these latter receptors are essential for the development of neural crest-derived cell lineage, enteric neuron and epidermal melanocytes. Isolation and characterization of endothelin-converting enzyme which cleaves big endothelin-1, an intermediate form, into mature endothelin-1 has revealed a type II integral membrane-bound metalloprotease that is structurally homologous to neutral endopeptidase. Development of selective inhibitors for endothelin-converting enzyme isoenzymes will facilitate a greater understanding of the role of endogenous endothelin isopeptides.

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