Lubiprostone has been used to treat chronic constipation and irritable bowel syndrome, and its mechanism of action has been attributed to the activation of chloride channel protein 2/cystic fibrosis transmembrane regulator (CIC-2/CFTR) chloride channels. This study examined the effects of lubiprostone on indomethacin-induced intestinal damage in male rats. Lubiprostone administration significantly reduced the severity of intestinal lesions, with the concomitant suppression of functional changes such as intestinal hypermotility, decreased mucus and fluid secretion, enterobacterial invasion, and upregulation of inducible nitric-oxide synthase and tumor necrosis factor α mRNAs. The effects of lubiprostone on the intestinal lesions and functional alterations were significantly abrogated by the coadministration of a selective EP4 antagonist, but not by a CFTR inhibitor. These results suggest that lubiprostone prevents indomethacin-induced enteropathy via an EP4 receptor-dependent mechanism not the CFTR/ClC-2 chloride channels.
See article at J Pharmacol Exp Ther 2014, 349:470–479.
- Copyright © 2014 by The American Society for Pharmacology and Experimental Therapeutics