Synergistic coronary vasoconstriction produced by endothelin-1 in combination with 5-hydroxytryptamine.
The present study was undertaken to examine the action of endothelin-1 (ET-1) per se, or the combined effects of ET-1 with vasoconstrictor agonists such as acetylcholine (ACh), histamine (His), and 5-hydroxytryptamine (5-HT), all of which have been implicated in the genesis of coronary spasm. Isometric tension development and the cytosolic Ca2+ concentration [( Ca2+]i) in a ring segment of porcine coronary artery loaded with fura-2 were measured simultaneously with a mechanoelectric transducer and a fluorometer, respectively. ET-1 (30-100 pM) specifically potentiated the 5-HT-induced contraction without causing a significant increase in [Ca2+]i. This effect of the peptide seems to be qualitatively similar to that produced by the tumor-promoting phorbol ester, DPB. These results suggest that the combined stimulation of ET-1 and 5-HT augments the Ca2+ sensitivity of the contractile elements through the possible activation of protein kinase C.
Nakayama
K
K
Department of Pharmacology, University of Shizuoka, School of Pharmaceutical Sciences, Japan.
Ishigai
Y
Y
Uchida
H
H
Tanaka
Y
Y
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism; D003331:Coronary Vessels / Q000187:drug effects*; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D004357:Drug Synergism; D016232:Endothelins / Q000494:pharmacology*; D016257:Fura-2; D066298:In Vitro Techniques; D009119:Muscle Contraction / Q000187:drug effects; D010703:Phorbol Esters / Q000494:pharmacology; D012701:Serotonin / Q000494:pharmacology*; D013552:Swine; D014661:Vasoconstriction / Q000187:drug effects*
D016232:Endothelins; D010703:Phorbol Esters; C039067:12-deoxyphorbol 13-isobutyrate; D012701:Serotonin; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D002118:Calcium; D016257:Fura-2