title: The contribution of protein kinase C and CPI-17 signaling pathways to hypercontractility in murine experimental colitis.
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(H) 2 colitis in BALB/c mice.
  
  
  METHODS
  Colitis was induced in BALB/c mice by provision of 5% dextran sodium sulfate (DSS) for 7 days. 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.
  
  
  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
  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.
authors.affiliation: Smooth Muscle and Gastrointestinal Research Groups, Department of Biochemistry & Molecular Biology, Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada.
authors.forename: E
authors.initials: E
authors.lastname: Ihara
authors.forename: M
authors.initials: M
authors.lastname: Chappellaz
authors.forename: S R
authors.initials: SR
authors.lastname: Turner
authors.forename: J A
authors.initials: JA
authors.lastname: MacDonald
mesh_terms: D000818:Animals; D002217:Carbachol / Q000494:pharmacology; D018679:Cholinergic Agonists / Q000494:pharmacology; D003092:Colitis / Q000139:chemically induced* / Q000503:physiopathology*; D003106:Colon / Q000033:anatomy & histology / Q000502:physiology*; D005260:Female; D047908:Intracellular Signaling Peptides and Proteins; D007527:Isoenzymes / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology*; D009124:Muscle Proteins; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology; D010749:Phosphoprotein Phosphatases / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D018679:Cholinergic Agonists; D047908:Intracellular Signaling Peptides and Proteins; D007527:Isoenzymes; D009124:Muscle Proteins; C107507:PPP1R14A protein, human; D047428:Protein Kinase Inhibitors; D002217:Carbachol; D011493:Protein Kinase C; D010749:Phosphoprotein Phosphatases