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 Citations (Scopus)

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)
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Volume281
Issue number2 44-2
StatePublished - 2001

Fingerprint

Myosin-Light-Chain Kinase
Lower Esophageal Sphincter
Protein Kinase C
Esophagus
Smooth Muscle
Calmodulin-Binding Proteins
Phosphotransferases
Myosin Light Chains
Phosphorylation
Calcium-Calmodulin-Dependent Protein Kinases
Protein C Inhibitor
Protein Kinase Inhibitors
Smooth Muscle Myocytes

Keywords

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

ASJC Scopus subject areas

  • Gastroenterology
  • Physiology
  • Physiology (medical)

Cite this

Myosin light chain kinase- and PKC-dependent contraction of LES and esophageal smooth muscle. / Sohn, U. D.; Cao, Weibiao; Tang, Da Chun; Stull, J. T.; Haeberle, J. R.; Wang, C. L A; Harnett, K. M.; Behar, J.; Biancani, P.

In: American Journal of Physiology - Gastrointestinal and Liver Physiology, Vol. 281, No. 2 44-2, 2001.

Research output: Contribution to journalArticle

Sohn, UD, Cao, W, Tang, DC, Stull, JT, Haeberle, JR, Wang, CLA, Harnett, KM, 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, vol. 281, no. 2 44-2.
Sohn, U. D. ; Cao, Weibiao ; Tang, Da Chun ; Stull, J. T. ; Haeberle, J. R. ; Wang, C. L A ; Harnett, K. M. ; Behar, J. ; Biancani, P. / Myosin light chain kinase- and PKC-dependent contraction of LES and esophageal smooth muscle. In: American Journal of Physiology - Gastrointestinal and Liver Physiology. 2001 ; Vol. 281, No. 2 44-2.
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AU - Cao, Weibiao

AU - Tang, Da Chun

AU - Stull, J. T.

AU - Haeberle, J. R.

AU - Wang, C. L A

AU - Harnett, K. M.

AU - Behar, J.

AU - Biancani, P.

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AB - 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.

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