Pathophysiology of the endothelin system - lessons from genetically manipulated animal models.

摘要: Shortly after discovery of ET-1 in 1988, the entire endothelin system was characterized. The consists three peptides ET-1, ET-2 and ET-3, their G-protein-coupled receptors receptor A B (ETRA ETRB) two endothelin-converting enzymes (ECE-1 ECE-2). Genetically modified animal models are an important tool biomedical research. Here we describe key findings obtained from genetically either over-expressing compounds ET or lacking these (knockout mice). Results different transgenic knockout disclose that plays a major role embryonic development. Two system-dependent neural crest-driven developmental pathways become obvious: one them being ET-1/ETAR axis, responsible for cardio-renal function development as well cranial development; other seems to be ET-3/ETBR mediated signalling pathway. Mutations within this axis associated with disruptions epidermal melanocytes enteric neurons. These led similar humans Hirschsprung disease. In adult life is most cardiovascular fibrotic remodelling heart, lung kidney regulation water salt excretion.