Endothelin-1 stimulates phosphatidylinositol hydrolysis and calcium uptake in isolated canine coronary arteries

Journal Article · Sun Jan 01 04:00:00 EST 1989 · J. Cardiovasc. Pharmacol.; (United States)

DOI:https://doi.org/10.1097/00005344-198900135-00018· OSTI ID:5822276

Pang, D C; Johns, A; Patterson, K; Botelho, L H; Rubanyi, G M

The effects of synthetic endothelin-1 (ET-1) (10(-10)-3 x 10(-7) M) on isometric force, /sup 45/Ca2+ uptake, and phosphatidylinositol (PI) hydrolysis were determined in isolated canine coronary artery rings. ET-1 caused contraction and stimulated /sup 45/Ca2+ uptake and PI hydrolysis (determined as inositol monophosphate accumulation) in a concentration-dependent manner with EC50 values of 6.3 x 10(-9), 2 x 10(-9), and 3 x 10(-9) M, respectively. Maximal responses were obtained with 3 x 10(-8) M ET-1 for all three parameters. At the maximally effective concentration, ET-1 caused a 1.8-fold increase in the rate of /sup 45/Ca2+ uptake following a 1-min exposure (the shortest time point tested) while the contractile response reached maximum only after 6 min. ET-1 (3 x 10(-8) M) stimulated a biphasic accumulation of inositol monophosphate with an initial rapid 1.4-fold increase detectable between 30 and 60 s followed by a secondary 11.9-fold increase at 30 min. These data show that PI hydrolysis and Ca2+ uptake are early events in the action of ET-1 on coronary artery vascular smooth muscle that precede the maximal contractile response. It is suggested that all of these responses are triggered by the interaction of ET-1 with a cell-surface receptor.

• Research Organization: Berlex Laboratories, Inc., Cedar Knolls, NJ (USA)
• OSTI ID: 5822276
• Journal Information: J. Cardiovasc. Pharmacol.; (United States), Journal Name: J. Cardiovasc. Pharmacol.; (United States) Vol. 13 Suppl 5; ISSN JCPCD
• Country of Publication: United States
• Language: English

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59 BASIC BIOLOGICAL SCIENCES
ALKALINE EARTH ISOTOPES
ALKALINE EARTH METALS
ANIMALS
ARTERIES
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BIOCHEMICAL REACTION KINETICS
BLOOD VESSELS
BODY
CALCIUM
CALCIUM 45
CALCIUM ISOTOPES
CARDIOVASCULAR AGENTS
CARDIOVASCULAR SYSTEM
CONTRACTION
CORONARIES
DAYS LIVING RADIOISOTOPES
DOGS
DOSE-RESPONSE RELATIONSHIPS
DRUGS
ELEMENTS
ESTERS
EVEN-ODD NUCLEI
IN VITRO
INTERMEDIATE MASS NUCLEI
ISOTOPE APPLICATIONS
ISOTOPES
KINETICS
LIPIDS
MAMMALS
MEMBRANE PROTEINS
MEMBRANE TRANSPORT
METABOLISM
METALS
MUSCLES
NUCLEI
ORGANIC COMPOUNDS
ORGANIC PHOSPHORUS COMPOUNDS
ORGANS
PEPTIDES
PHOSPHOLIPIDS
PROTEINS
RADIOISOTOPES
REACTION KINETICS
RECEPTORS
TRACER TECHNIQUES
VASOCONSTRICTORS
VERTEBRATES