抄録
Blebbistatin, a potent inhibitor of striated muscle myosin II and vertebrate nonmuscle myosin II, is known to poorly inhibit the smooth muscle myosin ATPase activity (Limouze et al., 2004). Recent studies using intact smooth muscle preparations (e.g. Rhee et al., 2006) presented inhibitory effects of blebbistatin on the contraction at least in some experimental conditions, however. We, therefore, studied the effects of blebbistatin on the mechanical responses of beta escin skinned preparations of taenia caeci and carotid artery from guinea pig, to evaluate the blebbistatin action on the smooth muscle contractile elements in detail. Blebbistatin inhibited both Ca2+-induced contraction with only little effects on the Ca2+ sensitivity for the force, and 30 mM Mg2+ induced, myosin phosphorylation independent, force development. Also blebbistatin strongly suppressed ATP-induced force generation in thiophosphorylated preparations. These effects of blebbistatin were highly temperature dependent. Also, blebbistatin accelerated relaxation by Ca2+. IC50 values of the blebbistatin effects presented above were nearly 20 micro M. We also found that blebbistatin inhibited the "native" gizzard myosin ATPase activitiy at about 20 micro M. The present results suggested that blebbistain directly interfare cross-bridge interaction in phasic and tonic smooth muscle through inhibition of the smooth muscle myosin ATPase. [J Physiol Sci. 2007;57 Suppl:S67]
