Potent Inhibition of Arterial Smooth Muscle Tonic Contractions by the Selective Myosin II Inhibitor, Blebbistatin
| Autor: | Arthur S. Rovner, Amy S. Miner, Paul H. Ratz, Daniel P. Meer, Thomas J. Eddinger, Joel T. Meehl |
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| Rok vydání: | 2006 |
| Předmět: |
Gene isoform
Vascular smooth muscle chemistry.chemical_element macromolecular substances Biology Calcium Heterocyclic Compounds 4 or More Rings Muscle Smooth Vascular Potassium Chloride Tonic (physiology) Myosin medicine Animals Actin Myosin Type II Pharmacology Cell biology medicine.anatomical_structure Biochemistry chemistry Vasoconstriction Molecular Medicine Phosphorylation Female Rabbits Chickens Artery |
| Zdroj: | Journal of Pharmacology and Experimental Therapeutics. 320:865-870 |
| ISSN: | 1521-0103 0022-3565 |
| Popis: | Blebbistatin is reported to be a selective and specific small molecule inhibitor of the myosin II isoforms expressed by striated muscles and nonmuscle (IC(50) = 0.5-5 microM) but is a poor inhibitor of purified turkey smooth muscle myosin II (IC(50) approximately 80 microM). We found that blebbistatin potently (IC(50) approximately 3 microM) inhibited the actomyosin ATPase activities of expressed "slow" [smooth muscle myosin IIA (SMA)] and "fast" [smooth muscle myosin IIB (SMB)] smooth muscle myosin II heavy-chain isoforms. Blebbistatin also inhibited the KCl-induced tonic contractions produced by rabbit femoral and renal arteries that express primarily SMA and the weaker tonic contraction produced by the saphenous artery that expresses primarily SMB, with an equivalent potency comparable with that identified for nonmuscle myosin IIA (IC(50) approximately 5 microM). In femoral and saphenous arteries, blebbistatin had no effect on unloaded shortening velocity or the tonic increase in myosin light-chain phosphorylation produced by KCl but potently inhibited beta-escin permeabilized artery contracted with calcium at pCa 5, suggesting that cell signaling events upstream from KCl-induced activation of cross-bridges were unaffected by blebbistatin. It is noteworthy that KCl-induced contractions of chicken gizzard were less potently inhibited (IC(50) approximately 20 microM). Adult femoral, renal, and saphenous arteries did not express significant levels of nonmuscle myosin. These data together indicate that blebbistatin is a potent inhibitor of smooth muscle myosin II, supporting the hypothesis that the force-bearing structure responsible for tonic force maintenance in adult mammalian vascular smooth muscle is the cross-bridge formed from the blebbistatin-dependent interaction between actin and smooth muscle myosin II. |
| Databáze: | OpenAIRE |
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