Abstract
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.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / pharmacology
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Action Potentials / drug effects
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Angiotensin II / pharmacology
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Animals
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Aorta, Thoracic / physiology
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Calcium / pharmacology
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Calcium Channel Blockers
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Calcium Channels / drug effects
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Calcium Channels / physiology*
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Cell Membrane / physiology
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Electrophysiology
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Endothelins
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Endothelium, Vascular
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Inositol 1,4,5-Trisphosphate
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Inositol Phosphates / metabolism
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Isradipine
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Oxadiazoles / metabolism
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Oxadiazoles / pharmacology
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Peptides / pharmacology*
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Phosphatidylinositols / metabolism
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Rats
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Rats, Inbred Strains
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Vasoconstriction / drug effects*
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Vasopressins / pharmacology
Substances
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Calcium Channel Blockers
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Calcium Channels
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Endothelins
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Inositol Phosphates
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Oxadiazoles
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Peptides
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Phosphatidylinositols
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Vasopressins
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Angiotensin II
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3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester
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Inositol 1,4,5-Trisphosphate
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Calcium
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Isradipine