Abstract

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 Ca 2+ mobilization in either the K +-depolarized or agonist activated swine carotid media at concentrations greater than 10 μM. Wortmannin reduced MRLC phosphorylation and stress to resting levels in stimulated tissues while Ca 2+ remained above resting levels. There was no evidence for Ca 2+ and MRLC phosphorylation-independent stress generation in swine arterial smooth muscle.

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