Cytochalasin D inhibits smooth muscle contraction by directly inhibiting contractile apparatus.
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.
Saito
S Y
SY
Department of Veterinary Pharmacology, Graduate School of Agriculture and Life Sciences, University of Tokyo, Japan.
Hori
M
M
Ozaki
H
H
Karaki
H
H
D000205:Actomyosin / Q000378:metabolism; D000818:Animals; D001011:Aorta / Q000187:drug effects; D017301:Ca(2+) Mg(2+)-ATPase / Q000378:metabolism; D002118:Calcium / Q000378:metabolism / Q000502:physiology; D002645:Chickens; D015638:Cytochalasin D / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D009638:Norepinephrine / Q000037:antagonists & inhibitors; D011188:Potassium / Q000037:antagonists & inhibitors; D051381:Rats; D017208:Rats, Wistar
D015638:Cytochalasin D; D000205:Actomyosin; D017301:Ca(2+) Mg(2+)-ATPase; D011188:Potassium; D002118:Calcium; D009638:Norepinephrine