Effect of Phorbol Esters on Cytosolic Ca^<2+> Level, Myosin Phosphorylation and Muscle Tension in High K^+ : Stimulated Bovine Tracheal Smooth Muscle

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To determine the role of protein kinase C (PKC)in bovine tracheal smooth muscle contractility, we examined the effects of phorbol esters on cytosolic Ca2+ level ([Ca2+]i), myosin light chain (MLC) phosphorylation and contractile force in intact muscle and contraction in a permeabilized preparation. In intact muscle, 12-deoxyphorbol 13-isobutyrate (DPB, 1 μM)increased the force without changing [Ca2+]i. High K+ (72.7 mM) induced sustained contraction with sustained increase in [Ca2+]i. In the muscle stimulated by high K+, 50 nM DPB increased the contractile force without changing [Ca2+]i, and 1 μM DPB increased the contractile force with decreasing [Ca2+]i. Thus DPB shifted the [Ca2+]i/force relationship for high K+ to the lower [Ca2+]i in a concentration-dependent manner. In permeabilized muscle, DPB did not induce contraction in the absence of Ca2+ (<<0 nM), but shifted the Ca2+/force relationship to the lower Ca2+ levels. In the muscle stimulated with high K+, DPB (50 nM and 1 μM)increased MLC phosphorylation and force without changing the MLC phosphorylation/force relationship. DPB (1 μM) increased PKC activity estimated by the translocation from the cytoplasm to the membrane. These results suggest that DPB increases the Ca2+ sensitivity of MLC phosphorylation via the activation of PKC. Furthermore, DPB at higher concentration has an inhibitory effect on stimulated [Ca2+]i.
社団法人日本薬理学会の論文
1997-06-01