Cytochalasin D Inhibits Smooth Muscle Contraction by Directly Inhibiting Contractile Apparatus

Abstract

We investigated the mode of relaxant effects of cytochalasin D, a capping agent of actin filaments, on contractile responses in the rat aorta and chicken gizzard smooth muscles.Cytochalasin D inhibited the contraction induced by high K⁺ or noradrenaline (10nM-1μM) without changing cytosolic Ca²⁺ level ([Ca²⁺] i) in the rat aorta. In the absence of external Ca²⁺, 12-deoxyphorbol 13-isobutylate (DPB) (1μM) induced sustained contraction without increasing in [Ca²⁺] i and cytochalasin D also inhibited this contraction. In the permeabilized chicken gizzard smooth muscle, cytochalasin D inhibited the Ca²⁺ (1-10μM)-induced contraction. Cytochalasin D also inhibited the Ca²⁺-independent contraction in the muscle which had been thiophosphorylated by ATP_γS. Cytochalasin D decreased the velocity of superprecipitation in the chicken gizzard native actomyosin (myosin B) affecting neither the level of MLC phosphorylation nor Mg²⁺-ATPase activity. These results suggest that cytochalasin D inhibits smooth muscle contractions without any effect on the Ca²⁺-dependent MLC phosphorylation or subsequent activation of myosin ATPase activity. Based on these evidences, it is concluded that cytochalasin D may inhibit smooth muscle contraction possiblly through uncoupling of the force generation from the activated actomyosin Mg²⁺-ATPase.