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

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 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 isozymes to the hypercontractile response was examined with pharmacological duanyu1531 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 duanyu1531 expression. Carbachol-induced peak (phasic) and sustained (tonic) contractions were increased. Chelerythrine was the most effective duanyu1531 inhibitor of both phasic and tonic contractions. There was no general difference in the percent contribution of conventional and novel duanyu1531 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 duanyu1531 isozymes contribute to the phasic and tonic contractile components of BALB/c colonic circular smooth muscle under normal conditions, with novel duanyu1531 isozymes having a greater contribution to the tonic contraction. However, no effect of inflammation was observed on the relative contribution of duanyu1531 and CPI-17 toward the observed hypercontractility.

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