Inhibition of Ca2+-dependent contraction in swine carotid artery by myosinkinase inhibitors

Experiments were designed to examine the efficacy of the MLCK inhibitors wo rtmannin and ML-9 in intact smooth muscle to determine whether contractile agonists can induce a Ca2+ and myosin light chain phosphorylation-independe nt contraction. Both wortmannin and ML-9 reduced active stress in a dose-de pendent manner. Both inhibitors interfered with Ca2+ mobilization in either the K+-depolarized or agonist activated swine carotid media at concentrati ons greater than 10 mu M 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. (C) 1999 Elsevier Scien ce Inc. All rights reserved.