Inhibition of Ca2+-dependent contraction in swine carotid artery by myosin kinase inhibitors.
Experiments were designed to examine the efficacy of the MLCK inhibitors wortmannin and ML-9 in intact smooth muscle to determine whether contractile agonists can induce a Ca(2+) and myosin light chain phosphorylation-independent contraction. Both wortmannin and ML-9 reduced active stress in a dose-dependent manner. Both inhibitors interfered with Ca2+ mobilization in either the K(+)-depolarized or agonist activated swine carotid media at concentrations greater than 10 microM. Wortmannin reduced MRLC phosphorylation and stress to resting levels in stimulated tissues while Ca2+ remained above resting levels. There was no evidence for Ca2+ and MRLC phosphorylation-independent stress generation in swine arterial smooth muscle.
D000730:Androstadienes / Q000494:pharmacology*; D000818:Animals; D001381:Azepines / Q000494:pharmacology*; D002118:Calcium / Q000737:chemistry; D002339:Carotid Arteries / Q000187:drug effects / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006632:Histamine / Q000494:pharmacology; D006801:Humans; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009219:Myosin-Light-Chain Kinase / Q000037:antagonists & inhibitors*; D010766:Phosphorylation / Q000187:drug effects; D013552:Swine; D014661:Vasoconstriction / Q000187:drug effects*; D014664:Vasodilation / Q000187:drug effects; D000077191:Wortmannin