(-)-Blebbistatin is a selective cell-permeable inhibitor of non-muscle myosin II ATPases and the active enantiomer of (+)-blebbistatin. It rapidly and reversibly inhibits Mg-ATPase activity and in vitro motility of non-muscle myosin IIA and IIB for several species (IC50 = 0.5-5 µM), while poorly inhibiting smooth muscle myosin (IC50 = 80 µM).
(-)-Blebbistatin selectively inhibits the ATPase activity of non-muscle myosin II[1][2].
体内研究
Blebbistatin effectively and dose-dependently relaxes both KCl- and carbachol-induced rat detrusor contractions as well as endothelin-1-induced human bladder contractions. Pre-incubation with 10 μM blebbistatin reduces carbachol responsiveness by 65% and inhibits electrical field stimulation-induced bladder contraction by 50% at 32 Hz[4].
体外研究
Blebbistatin effectively inhibits various striated muscle myosins and vertebrate nonmuscle myosin IIA and IIB, with IC50 values between 0.5 to 5 μM. It exhibits much weaker inhibition of smooth muscle myosin, with an IC50 of 80 μM[1].
Blebbistatin does not interfere with nucleotide binding to the skeletal muscle myosin subfragment-1. Instead, it preferentially binds to the ATPase intermediate that has ADP and phosphate at the active site, thereby slowing down phosphate release. This inhibitor traps the myosin heads in a products complex that exhibits low affinity for actin[2].
In culture-activated hepatic stellate cells, blebbistatin alters cell morphology and function. The stellate cells become smaller, develop a dendritic morphology, and show fewer myosin IIA-containing stress fibers and vinculin-containing focal adhesions. Blebbistatin hinders silicone wrinkle formation, diminishes collagen gel contraction, and blocks endothelin-1-induced intracellular Ca2+ release. Additionally, it enhances wound-induced cell migration[3].
作用机制
Blebbistatin blocked myosin II–dependent cell processes by blocking cell blebbing rapidly and reversibly as well as rapidly disrupted directed cell migration and cytokinesis in vertebrate cells.
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