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Impaired acetylcholine-induced smooth muscle contraction in colitis involves altered calcium mobilization and AKT

Ron W Wells1, Sandra Lourenssen, Michael G Blennerhassett

  • 1Gastrointestinal Diseases Research Unit, Kingston General Hospital and Queen's University, Kingston, Ontario, Canada.

Pflugers Archiv : European Journal of Physiology
|January 30, 2008
PubMed

Insights

Inflammation from trinitrobenzene sulphonic acid (TNBS) impairs colonic smooth muscle cell contraction by reducing calcium signaling and AKT activation. This study reveals AKT signaling as a key target during colitis.

Area of Science:

  • Gastroenterology
  • Cell Biology
  • Pharmacology

Background:

  • Trinitrobenzene sulphonic acid (TNBS)-induced colitis in rats affects circular smooth muscle cell (CSMC) contraction to acetylcholine (ACh).
  • The intracellular signaling pathways, including calcium and kinases like ERK1/2 and AKT, involved in this response during colitis are not well understood.

Purpose of the Study:

  • To investigate the role of intracellular calcium, AKT, and ERK1/2 signaling in CSMC response to ACh during TNBS-induced colitis.
  • To determine how inflammation and recovery impact these signaling pathways and smooth muscle function.

Main Methods:

  • Isolated colonic CSMC from control, TNBS-inflamed (day 4), and recovered (day 36) rats were stimulated with ACh.
  • Intracellular calcium levels and cell contraction were measured using fluorescence video microscopy.
  • Western blotting was employed to quantify total and phosphorylated AKT and ERK1/2 levels.

Main Results:

  • Colitis significantly reduced and delayed ACh-induced calcium elevation in CSMC.
  • ACh-induced contraction velocity was halved, with impaired calcium mobilization from intracellular stores.
  • While ACh increased AKT phosphorylation in control cells, this response was markedly reduced in colitis; AKT inhibition mimicked colitis-induced contraction deficits.

Conclusions:

  • TNBS-induced colitis impairs CSMC contraction by disrupting calcium signaling and reducing ACh-stimulated AKT phosphorylation.
  • AKT signaling is identified as a critical pathway affected by inflammation, contributing to impaired colonic smooth muscle function during colitis.

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