The contribution of protein kinase C and CPI-17 signaling pathways to hypercontractility in murine experimental colitis

E. Ihara, M. Chappellaz, S. R. Turner, J. A. Macdonald

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Background Colonic smooth muscle contractility is altered in colitis, and several protein kinase pathways can mediate colonic smooth muscle contraction. In the present study, we investigated whether protein kinase C (PKC) pathways also play a role in colonic hypercontractility observed during T H2 colitis in BALB/c mice. Methods Colitis was induced in BALB/c mice by provision of 5% dextran sodium sulfate (DSS) for 7days. Changes in smooth muscle contractility were examined using dissected circular smooth muscle preparations from the distal colon. The contribution of conventional and novel PKC isozymes to the hypercontractile response was examined with pharmacological PKC inhibitors. Western blot analyses were used to examine protein expression and phosphorylation changes. Key Results Colonic smooth muscle was associated with inflammation-induced hypercontractility and altered PKC expression. Carbachol-induced peak (phasic) and sustained (tonic) contractions were increased. Chelerythrine was the most effective PKC inhibitor of both phasic and tonic contractions. There was no general difference in the percent contribution of conventional and novel PKC isozymes toward the DSS-induced hypercontractility, but inhibition of sustained force with GF109203x was higher for inflamed muscle. The CPI-17 phosphorylation was equally suppressed in both normal and DSS conditions by Gö6976 and chelerythrine, but only for the phasic component of contraction. Conclusions & Inferences The outcomes suggest that both conventional and novel PKC isozymes contribute to the phasic and tonic contractile components of BALB/c colonic circular smooth muscle under normal conditions, with novel PKC isozymes having a greater contribution to the tonic contraction. However, no effect of inflammation was observed on the relative contribution of PKC and CPI-17 toward the observed hypercontractility.

Original languageEnglish
Pages (from-to)e15-e26
JournalNeurogastroenterology and Motility
Volume24
Issue number1
DOIs
Publication statusPublished - Jan 1 2012
Externally publishedYes

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Colitis
Protein Kinase C
Smooth Muscle
Dextran Sulfate
Isoenzymes
Protein C Inhibitor
Protein Kinase Inhibitors
Phosphorylation
Inflammation
cyclopropapyrroloindole
Carbachol
Muscle Contraction
Protein Kinases
Colon
Western Blotting
Pharmacology
Muscles

All Science Journal Classification (ASJC) codes

  • Physiology
  • Endocrine and Autonomic Systems
  • Gastroenterology

Cite this

The contribution of protein kinase C and CPI-17 signaling pathways to hypercontractility in murine experimental colitis. / Ihara, E.; Chappellaz, M.; Turner, S. R.; Macdonald, J. A.

In: Neurogastroenterology and Motility, Vol. 24, No. 1, 01.01.2012, p. e15-e26.

Research output: Contribution to journalArticle

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AB - Background Colonic smooth muscle contractility is altered in colitis, and several protein kinase pathways can mediate colonic smooth muscle contraction. In the present study, we investigated whether protein kinase C (PKC) pathways also play a role in colonic hypercontractility observed during T H2 colitis in BALB/c mice. Methods Colitis was induced in BALB/c mice by provision of 5% dextran sodium sulfate (DSS) for 7days. Changes in smooth muscle contractility were examined using dissected circular smooth muscle preparations from the distal colon. The contribution of conventional and novel PKC isozymes to the hypercontractile response was examined with pharmacological PKC inhibitors. Western blot analyses were used to examine protein expression and phosphorylation changes. Key Results Colonic smooth muscle was associated with inflammation-induced hypercontractility and altered PKC expression. Carbachol-induced peak (phasic) and sustained (tonic) contractions were increased. Chelerythrine was the most effective PKC inhibitor of both phasic and tonic contractions. There was no general difference in the percent contribution of conventional and novel PKC isozymes toward the DSS-induced hypercontractility, but inhibition of sustained force with GF109203x was higher for inflamed muscle. The CPI-17 phosphorylation was equally suppressed in both normal and DSS conditions by Gö6976 and chelerythrine, but only for the phasic component of contraction. Conclusions & Inferences The outcomes suggest that both conventional and novel PKC isozymes contribute to the phasic and tonic contractile components of BALB/c colonic circular smooth muscle under normal conditions, with novel PKC isozymes having a greater contribution to the tonic contraction. However, no effect of inflammation was observed on the relative contribution of PKC and CPI-17 toward the observed hypercontractility.

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