Journal
NEUROGASTROENTEROLOGY AND MOTILITY
Volume 21, Issue 11, Pages 1218-1221Publisher
WILEY
DOI: 10.1111/j.1365-2982.2009.01353.x
Keywords
colon; nociception; protease-activated receptor; visceral hyperalgesia
Funding
- Canadian Institutes of Health Research
- Crohn's & Colitis Foundation of Canada
- GIDRU Canadian Institutes of Health Research
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P>The antinociceptive mechanism underlying protease-activated receptor-4 (PAR(4)) activation was studied in Fast Blue-labelled dorsal root ganglia (DRG) neurons from mouse colon which expressed transcript for PAR(4). Whole cell perforated patch clamp recordings were obtained from these neurons and the effects on neuronal excitability of PAR(4) activating peptides (AP) and reverse peptides (RP) were examined. A 3-min application of PAR(4)-AP (100 mu mol L-1) markedly suppressed the number of action potential discharged at twice rheobase for up to 60 min. PAR(4)-RP had no effect. PAR(4) application suppresses the excitatory effects of PAR(2). These findings demonstrated that activation of PAR(4) on colonic DRG neurons suppresses their excitability, suggesting these receptors could provide important targets for modifying pain in colonic GI disorders such as IBS and IBD.
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