Proteinases and proteinase-activated receptor 2: a possible role to promote visceral hyperalgesia in rats

Gastroenterology
Anne-Marie CoelhoLionel Bueno

Abstract

PAR-2s are highly expressed throughout the gastrointestinal tract. These receptors are cleaved by trypsin and mast cell tryptase and can be activated by peptides corresponding to the tethered ligand of the receptor (SLIGRL-NH2 for rat). The aim of this study was to determine whether colonic administration of PAR-2 agonists affects visceral sensitivity to rectal distention in conscious rats. Abdominal contractions (a criteria of visceral pain) were recorded in rats equipped with intramuscular electrodes. Rectal distention was performed at various times after intracolonic infusion of SLIGRL-NH2 and trypsin. Inflammation parameters and permeability were followed in the colon after the intracolonic injections. Fos expression at a spinal level (L4-L6) was also studied 2 hours after intracolonic injection of SLIGRL-NH2. Rectal distention significantly increased abdominal contractions starting at the RD volume of 0.8 mL. Intracolonic injection of SLIGRL-NH2 (200 microg/rat) and trypsin (200 U/rat), but not vehicle, LRGILS-NH2 (control peptide), boiled trypsin, or SLIGRL-NH2 injected IP, significantly increased (P < 0.05) abdominal contractions for high volumes of distention, 10- and 24-hour postinfusion. SLIGRL-NH2-induced hyperalgesi...Continue Reading

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