Molecular mechanism of action of the vasoconstrictor peptide endothelin

• Published in: Biochemical and biophysical research communications Vol. 157; no. 3; p. 977
• Main Authors: Van Renterghem, C, Vigne, P, Barhanin, J, Schmid-Alliana, A, Frelin, C, Lazdunski, M
• Format: Journal Article
• Language: English
• Published: United States 30-12-1988
• Subjects: 3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester - pharmacology; Action Potentials - drug effects; Angiotensin II - pharmacology; Animals; Aorta, Thoracic - physiology; Calcium - pharmacology; Calcium Channel Blockers; Calcium Channels - drug effects; Calcium Channels - physiology; Cell Membrane - physiology; Electrophysiology; Endothelins; Endothelium, Vascular; Inositol 1,4,5-Trisphosphate; Inositol Phosphates - metabolism; Isradipine; Oxadiazoles - metabolism; Oxadiazoles - pharmacology; Peptides - pharmacology; Phosphatidylinositols - metabolism; Rats; Rats, Inbred Strains; Vasoconstriction - drug effects; Vasopressins - pharmacology
• ISSN: 0006-291X
• DOI: 10.1016/S0006-291X(88)80970-7

Endothelin, one of the most potent vasoconstrictor known, has been suggested to act as an endogenous agonist of L-type Ca2+ channels. In this paper we show that endothelin stimulates the metabolism of inositol phosphates and induces the mobilization of intracellular Ca2+ stores. The transient activation of Ca2+-sensitive K+ channel provokes an hyperpolarization of the membrane. It is followed by a sustained depolarization which is due to the opening of a non-specific cation channel which is permeable to Ca2+ and Mg2+. The depolarization then activates L-type Ca2+ channels. This mechanism of action explains why part of the endothelin-induced vasocontriction is eliminated by L-type Ca2+ channel blockers.