(±)-Blebbistatin is a racemic mixture containing two configurations, (+)-Blebbistatinb and (-)-Blebbistatin (Cat. No. GC13430). (±)-Blebbistatin can effectively inhibit the activity of non-muscle myosin II ATPase and the expression of various striated muscle myosins and non-muscle myosins in vertebrates[1, 2]. (±)-Blebbistatin is a commonly used excitation-contraction uncoupling agent in cardiovascular physiology[3]. (±)-Blebbistatin is a potential photodynamic drug that can kill cancer cells. Exposure to UV light with a wavelength below 488nm can also lead to rapid inhibition of (±)-Blebbistatin[4].
In vitro, (±)-Blebbistatin (0.1, 0.5, 2, 10μM) treated rat ventricular myocytes for 10min prevented cell shortening in a dose-dependent manner with an IC50 of 0.43μM, but did not affect intracellular calcium transients ([Ca2+]i)[5].
In vivo, (±)-Blebbistatin (125nM/kg) treated rats with detrusor overactivity (DO) by intravesical instillation significantly reduced the detrusor overactivity index, non-micturition contraction amplitude, and non-micturition contraction frequency, and improved urine storage without impairing urination function[6]. (±)-Blebbistatin (125nM/kg) treated DO rats by intra-arterial injection attenuated 13-cis-RA-induced changes in cystometric parameters and central and peripheral neurotrophic factor levels, and also had antidepressant-like effects[7].
References:
[1]Lucas‐Lopez C, Patterson S, Blum T, et al. Absolute Stereochemical Assignment and Fluorescence Tuning of the Small Molecule Tool,(–)‐Blebbistatin[J]. 2005.
[2]Limouze J, Straight A F, Mitchison T, et al. Specificity of blebbistatin, an inhibitor of myosin II[J]. Journal of Muscle Research & Cell Motility, 2004, 25: 337-341.
[3]George S A , Lin Z , Efimov I R .Simultaneous triple-parametric optical mapping of transmembrane potential, intracellular calcium and NADH for cardiac physiology assessment[J].Communications Biology, 2024.
[4]Sakamoto T, Limouze J, Combs C A, et al. Blebbistatin, a myosin II inhibitor, is photoinactivated by blue light[J]. Biochemistry, 2005, 44(2): 584-588.
[5]Fedorov V V, Lozinsky I T, Sosunov E A, et al. Application of blebbistatin as an excitation–contraction uncoupler for electrophysiologic study of rat and rabbit hearts[J]. Heart rhythm, 2007, 4(5): 619-626.
[6]Wróbel A, Nowakowski Ł, Doboszewska U, et al. Blebbistatin reveals beneficial effects on the cystometric parameters in an animal model of detrusor overactivity[J]. Naunyn-schmiedeberg's Archives of Pharmacology, 2019, 392: 843-850.
[7]Wróbel A, Doboszewska U, Rechberger E, et al. Blebbistatin, a myosin II inhibitor, exerts antidepressant-like activity and suppresses detrusor overactivity in an animal model of depression coexisting with overactive bladder[J]. Neurotoxicity Research, 2019, 35: 196-207.
(±)-Blebbistatin是一种外消旋体混合物，其中包含(+)-Blebbistatinb和(-)-Blebbistatin（货号：GC13430）两种构型。(±)-Blebbistatin能够有效抑制非肌肉肌球蛋白II ATP酶活性，抑制多种横纹肌肌球蛋白以及脊椎动物非肌肉肌球蛋白表达[1, 2]。(±)-Blebbistatin是一种心血管生理学中常用的激发-收缩解偶联剂[3]。(±)-Blebbistatin是一种潜在的光动力药物，可以杀死癌细胞，暴露于波长低于488nm的UV光也可导致(±)-Blebbistatin迅速被抑制[4]。
在体外，(±)-Blebbistatin（0.1, 0.5, 2, 10μM）处理大鼠心室肌细胞10min，以剂量依赖性方式阻止细胞缩短，IC50为0.43µM，但不会影响细胞内钙瞬变（[Ca2+]i）[5]。
在体内，(±)-Blebbistatin（125nM/kg）通过膀胱灌注治疗患有逼尿肌过度活动（DO）的大鼠，显著降低了逼尿肌过度活动指数、非排尿收缩幅度和非排尿收缩频率，改善尿液储存，而不会损害排尿功能[6]。(±)-Blebbistatin（125nM/kg）通过动脉注射治疗DO大鼠，可减弱13-cis-RA诱导的膀胱测压参数以及中枢和外周神经营养因子水平的变化，还具有抗抑郁样作用[7]。