Wortmannin inhibits the myofilament Ca2+ sensitization induced by endothelin-1.
Endothelin-1 induces a positive inotropic effect due to a combination of an increase in Ca2+ transients and myofilament Ca2+ sensitivity in rabbit ventricular myocardium. We carried out the experiments to examine the potential contribution of myosin light chain kinase to the Ca2+ sensitization induced by endothelin-1 by use of wortmannin that inhibits myosin light chain kinase at high concentrations (IC50=200 nM). Wortmannin at 3 microM suppressed the basal force of contraction, but did not affect the positive inotropic effect mediated by beta-adrenoceptors. Wortmannin at 1 and 3 microM markedly inhibited the positive inotropic effect of endothelin-1, but did not affect the increase in Ca2+ transients elicited by endothelin-1. The present findings imply that the increase in myofilament Ca2+ sensitivity induced by endothelin-1 may be in part due to activation of myosin light chain kinase in rabbit ventricular myocardium.
Chu
Li
L
Department of Cardiovascular Pharmacology, Yamagata University School of Medicine, Yamagata 990-9585, Japan.
Endoh
Masao
M
D008841:Actin Cytoskeleton / Q000187:drug effects* / Q000502:physiology; D000730:Androstadienes / Q000494:pharmacology*; D000818:Animals; D020013:Calcium Signaling / Q000187:drug effects* / Q000502:physiology; D048429:Cell Size / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D019332:Endothelin-1 / Q000494:pharmacology*; D066298:In Vitro Techniques; D011817:Rabbits; D000077191:Wortmannin
D000730:Androstadienes; D019332:Endothelin-1; D000077191:Wortmannin