Inhibitory Effect of Forskolin on Myosin Phosphorylation-Dependent and Independent Contractions in Bovine Tracheal Smooth Muscle.
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- TAJIMI Masaomi
- Department of Veterinary Pharmacology, Graduate School of Agriculture
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- HORI Masatoshi
- Department of Veterinary Pharmacology, Graduate School of Agriculture
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- MITSUI Minori
- Department of Veterinary Pharmacology, Graduate School of Agriculture
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- OZAKI Hiroshi
- Life Sciences, The University of Tokyo
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- KARAKI Hideaki
- Life Sciences, The University of Tokyo
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抄録
In bovine tracheal smooth muscle, carbachol (CCh, 1μM) and high K+ (72.7mM) induced sustained increases in cytosolic Ca2+level ([Ca2+] i), myosin light chain (MLC) phosphorylation and force of contraction. Forskolin (FK, 1-10μM) inhibited the CCh-induced increase in [Ca2+MLC phosphorylation and force in parallel. In contrast, FK inhibited the high K+-induced contraction and MLC phosphorylation without changing [Ca2+]In the absence of extracellular Ca2+ (with 0.5mM EGTA), CCh (10μM) and caffeine (20mM) induced transient increase in [Ca2+] i and contractile force by releasing Ca2+from cellular store. FK strongly inhibited the CCh-induced Ca2+transient, but failed to inhibit the caffeine-induced Ca2+transient. In the absence of external Ca2+, 12-deoxyphorbol 13-isobutylate (DPB, 1μM) induced sustained contraction without increase in [Ca2+] and MLC phosphorylation. FK inhibited this contraction without changing [Ca2+] In permeabilized muscle, Ca2+induced contraction in a concentration-dependent manner. FK (10μM) and cAMP (1-100μM) shifted the Ca2+-force curve to the higher Ca2+levels. CCh with GTP, GTPyS or DPB enhanced contraction in the presence of constant level of Ca2+. Forskolin and cAMP also inhibited the enhanced contractions in the permeabilized muscle. In the permeabilized, thiophosphorylated muscle, ATP induced contraction in the absence of Ca2+. cAMP (300μM) had no effect on this contraction. These results suggest that forskolin inhibits agonist-induced contraction in tracheal smooth muscle by multiple mechanisms of action; 1) inhibition of MLC phosphorylation by reducing Ca2+influx and Ca2+release, 2) inhibition of MLC phosphorylation by changing the MLC kinase/phosphatase balance, and 3) inhibition of regulatory mechanism which is not dependent on MLC phosphorylation.
収録刊行物
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- Ｊｏｕｒｎａｌ ｏｆ Ｓｍｏｏｔｈ Ｍｕｓｃｌｅ Ｒｅｓｅａｒｃｈ
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Ｊｏｕｒｎａｌ ｏｆ Ｓｍｏｏｔｈ Ｍｕｓｃｌｅ Ｒｅｓｅａｒｃｈ 31 (4), 129-142, 1995
日本平滑筋学会