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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Author(s)

Abstract

To determine the role of protein kinase C (PKC)in bovine tracheal smooth muscle contractility, we examined the effects of phorbol esters on cytosolic Ca<SUP>2+</SUP> level ([Ca<SUP>2+</SUP>]<SUB>i</SUB>), 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 [Ca<SUP>2+</SUP>]<SUB>i</SUB>. High K<SUP>+</SUP> (72.7 mM) induced sustained contraction with sustained increase in [Ca<SUP>2+</SUP>]<SUB>i</SUB>. In the muscle stimulated by high K<SUP>+</SUP>, 50 nM DPB increased the contractile force without changing [Ca<SUP>2+</SUP>]<SUB>i</SUB>, and 1 μM DPB increased the contractile force with decreasing [Ca<SUP>2+</SUP>]<SUB>i</SUB>. Thus DPB shifted the [Ca<SUP>2+</SUP>]<SUB>i</SUB>/force relationship for high K<SUP>+</SUP> to the lower [Ca<SUP>2+</SUP>]<SUB>i</SUB> in a concentration-dependent manner. In permeabilized muscle, DPB did not induce contraction in the absence of Ca<SUP>2+</SUP> (<<0 nM), but shifted the Ca<SUP>2+</SUP>/force relationship to the lower Ca<SUP>2+</SUP> levels. In the muscle stimulated with high K<SUP>+</SUP>, 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 Ca<SUP>2+</SUP> sensitivity of MLC phosphorylation via the activation of PKC. Furthermore, DPB at higher concentration has an inhibitory effect on stimulated [Ca<SUP>2+</SUP>]<SUB>i</SUB>.

Journal

  • The Japanese Journal of Pharmacology

    The Japanese Journal of Pharmacology 74(2), 195-201, 1997-06-01

    The Japanese Pharmacological Society

References:  20

Cited by:  1

Codes

  • NII Article ID (NAID)
    10008678988
  • NII NACSIS-CAT ID (NCID)
    AA00691188
  • Text Lang
    ENG
  • Article Type
    Journal Article
  • ISSN
    00215198
  • NDL Article ID
    4260349
  • NDL Source Classification
    ZS51(科学技術--薬学)
  • NDL Call No.
    Z53-D199
  • Data Source
    CJP  CJPref  NDL  J-STAGE 
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