title: Endothelin-1-dependent signaling pathways in the myocardium.
abstract: Endothelin-1 (ET-1) is a locally acting vasoactive peptide that also has profound effects on the contractile properties and growth of the cardiac myocyte. Binding of ET-1 to its transmembrane heptahelical receptors activates G proteins of the G(q) and G(i) classes. Activation of G(q) stimulates hydrolysis of phosphatidylinositol-4,5-bisphosphate, and the diacylglycerol thus formed stimulates protein kinase C. Subsequently, the protein kinase Raf is activated and this leads to activation of the extracellular signal-regulated protein kinase (ERK) subfamily of mitogen-activated protein kinases. Activation of G(i) counteracts β-adrenoceptor-mediated increases in cAMP concentrations. We have attempted to rationalize the established physiological consequences of ET-1 agonism in the cardiac myocyte (that is, on contraction and growth) in terms of activation of these signaling pathways.
authors.affiliation: Peter H. Sugden is at the National Heart and Lung Institute (Cardiac Medicine), Imperial College of Science, Technology and Medicine, London SW3 6LY, United Kingdom.
authors.forename: P H
authors.initials: PH
authors.lastname: Sugden
authors.forename: M A
authors.initials: MA
authors.lastname: Bogoyevitch