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J Smooth Muscle Res. 1996 Apr;32(2):51-60.

Cytochalasin D inhibits smooth muscle contraction by directly inhibiting contractile apparatus.

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1
Department of Veterinary Pharmacology, Graduate School of Agriculture and Life Sciences, University of Tokyo, Japan.

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 (10 nM-1 microM) without changing cytosolic Ca2+ level ([Ca2+]i) in the rat aorta. In the absence of external Ca2+, 12-deoxyphorbol 13-isobutylate (DPB) (1 microM) 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+ (1-10 microM)-induced contraction. Cytochalasin D also inhibited the Ca(2+)-independent contraction in the muscle which had been thiophosphorylated by ATP gamma S. Cytochalasin D decreased the velocity of superprecipitation in the chicken gizzard native actomyosin (myosin B) affecting neither the level of MLC phosphorylation nor Mg(2+)-ATPase activity. These results suggest that cytochalasin D inhibits smooth muscle contractions without any effect on the Ca(2+)-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 possibly through uncoupling of the force generation from the activated actomyosin Mg(2+)-ATPase.

PMID:
8845566
DOI:
10.1540/jsmr.32.51
[Indexed for MEDLINE]

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