Long-term downregulation of protease-activated receptor-2 expression in distal colon in rats following bacillary dysentery

The aim of this study was to determine changes of PAR-2 expression in distal colon and the sensitivity of colonic muscle to SLIGRL-NH2, the PAR-2-activating peptide (PAR-2-AP) following bacillary dysentery. Shigella flexneri was administrated intragastrically in healthy male rats to induce bacillary dysentery. The effect of SLIGRL-NH2 on the motility of colonic muscle strips were examined. The expression of PAR-2 was determined by immunohistochemistry and Western blotting. Intragastric administration of S. flexneri induced acute inflammation at the mucosa of the distal colon at 4-11 days, and the inflammation disappeared 18 days later. PAR-2-AP-induced TTX insensitive relaxation of the colonic muscle strips. This inhibitory effect on colonic circular muscle strips was reduced on days 11-35, but the carbachol-induced contraction did not change. PAR-2 was located at the colon smooth muscles cells and myenteric nerve plexus. The amount of PAR-2 expression in distal colon was down regulated on days 11-35. These data indicated that bacillary dysentery exerted a long-term downregulation on the expression of PAR-2 in distal colon. This might be the reason of the low sensitivity of the colon circular muscle strips to the PAR-2-AP-induced relaxation following intragastric administration of S. flexneri.