Myosin light chain kinase- and PKC-dependent contraction of LES and esophageal smooth muscle

U. D. Sohn, Weibiao Cao, Da Chun Tang, J. T. Stull, J. R. Haeberle, C. L A Wang, K. M. Harnett, J. Behar, P. Biancani

Research output: Contribution to journalArticle

30 Scopus citations

Abstract

In smooth muscle cells enzymatically isolated from circular muscle of the esophagus (ESO) and lower esophageal sphincter (LES), ACh-induced contraction and myosin light chain (MLC) phosphorylation were similar. Contraction and phosphorylation induced by purified MLC kinase (MLCK) were significantly greater in LES than ESO. ACh-induced contraction and MLC phosphorylation were inhibited by calmodulin and MLCK inhibitors in LES and by protein kinase C (PKC) inhibitors in ESO. Contraction of LES and ESO induced by the PKC agonist 1,2-dioctanoylglycerol (DG) was unaffected by MLCK inhibitors. Caldesmon and calponin concentration-dependently inhibited ACh-induced contraction of ESO and not LES. In ESO, caldesmon antagonist GS17C reversed caldesmon- but not calponin-induced ACh inhibition. GS17C caused contraction of permeabilized ESO but had much less effect on LES. GS17C-induced contraction was not affected by MLCK inhibitors, suggesting that MLCK may not regulate caldesmon-mediated contraction. DG-induced contraction of ESO and LES was inhibited by caldesmon and calponinin, suggesting that these proteins may regulate PKC-dependent contraction. We conclude that calmodulin and MLCK play a role in ACh-induced LES contraction, whereas the classical MLCK may not be the major kinase responsible for contraction and phosphorylation of MLC in ESO. ESO contraction is PKC dependent. Caldesmon and/or calponin may play a role in PKC-dependent contraction.

Original languageEnglish (US)
Pages (from-to)G467-G478
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Volume281
Issue number2 44-2
StatePublished - Aug 27 2001

Keywords

  • Calcium stores
  • Caldesmon
  • Calmodulin
  • Calponin
  • Cat
  • Second messenger system

ASJC Scopus subject areas

  • Physiology
  • Hepatology
  • Gastroenterology
  • Physiology (medical)

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    Sohn, U. D., Cao, W., Tang, D. C., Stull, J. T., Haeberle, J. R., Wang, C. L. A., Harnett, K. M., Behar, J., & Biancani, P. (2001). Myosin light chain kinase- and PKC-dependent contraction of LES and esophageal smooth muscle. American Journal of Physiology - Gastrointestinal and Liver Physiology, 281(2 44-2), G467-G478.