Vascular mechanism of action of endothelin-1: Effect of Ca2+ antagonists

Journal Article · Sat Dec 31 23:00:00 EST 1988 · Journal of Cardiovascular Pharmacology; (USA)

DOI:https://doi.org/10.1097/00005344-198900135-00009· OSTI ID:5405538

Chabrier, P E; Auguet, M; Roubert, P; Lonchampt, M O; Gillard, V; Guillon, J M; Delaflotte, S; Braquet, P ^[1]

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1. Institut Henri Beaufour, Les Ulis (France)

The vasoconstrictive properties of the endothelium-derived peptide, endothelin-1 (ET-1), were investigated on rat isolated aorta and on cultured rat aortic smooth muscle cells. In rat isolated aorta, endothelin-1 induced a slow and sustained contraction in a Ca2+-free medium; after calcium readmission, an additional sustained contraction was elicited. In vascular smooth muscle cells, endothelin-1 provoked a dose-dependent Ca2+ influx that was not inhibited by calcium entry blockers (nifedipine, D 600, or diltiazem). In these cells, ({sup 125}I)-endothelin-1 bound to a specific, saturable, and high affinity recognition site (Kd about 10(-9) M and Bmax = 52 +/- 2 fmol/10(6) cells). The binding was not reversible and not affected by calcium antagonists. These data do not support the hypothesis that endothelin-1 acts as an endogenous agonist of the voltage-dependent Ca2+ channels. The action of endothelin-1 can be separated into two components: one dependent on Ca2+ influx but insensitive to calcium antagonists and another independent of extracellular Ca2+. The irreversible binding of endothelin-1 may reflect an internalization of the ligand inside the cell membrane, leading to multiple contractile events.

• OSTI ID: 5405538
• Journal Information: Journal of Cardiovascular Pharmacology; (USA), Journal Name: Journal of Cardiovascular Pharmacology; (USA) Vol. 13 Suppl 5; ISSN 0160-2446; ISSN JCPCD
• Country of Publication: United States
• Language: English

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59 BASIC BIOLOGICAL SCIENCES
ALKALINE EARTH METAL COMPOUNDS
ALKALINE EARTH METALS
ANIMALS
AORTA
ARTERIES
BETA DECAY RADIOISOTOPES
BIOCHEMICAL REACTION KINETICS
BIOLOGICAL FUNCTIONS
BLOOD VESSELS
BODY
CALCIUM
CALCIUM COMPOUNDS
CARDIOVASCULAR AGENTS
CARDIOVASCULAR SYSTEM
CELL CONSTITUENTS
CELL CULTURES
CELL MEMBRANES
CONTRACTION
DAYS LIVING RADIOISOTOPES
DRUGS
ELECTRON CAPTURE RADIOISOTOPES
ELEMENTS
FUNCTIONS
IN VITRO
INTERMEDIATE MASS NUCLEI
IODINE 125
IODINE ISOTOPES
ISOTOPE APPLICATIONS
ISOTOPES
KINETICS
MAMMALS
MEMBRANE PROTEINS
MEMBRANE TRANSPORT
MEMBRANES
METALS
MUSCLES
NUCLEI
ODD-EVEN NUCLEI
ORGANIC COMPOUNDS
ORGANS
PEPTIDES
PORINS
PROTEINS
RADIOISOTOPES
RATS
REACTION KINETICS
RODENTS
TRACER TECHNIQUES
VASOCONSTRICTION
VASOCONSTRICTORS
VERTEBRATES