Su1871 Effects of DA-9701, a Prokinetic Agent on Gastric Motor Function in Guinea Pig; In Vivo and In Vitro Study

Abstract

ity was induced in twenty adult male Sprague-Dawley rats by butyrate enemas in the distal colon, and 10 control rats served as vehicle only. After butyrate enema, the rats were divided into 2 groups and were given respectively DA 9701 3mg/kg or vehicle. The rats were sacrificed at 1 and 2 days after treatment, and colonic damage score and tissue myeloperoxidase activity were evaluated. In lumbosacral L1 and L2 DRG, expression level of BDNF, ASIC 1a, ASIC 2b, IL-1β, and TNF-α were assessed using quantitative real-time PCR, ELISA, and western blot. Results: In L1 DRG, the levels of BDNF protein were increased at both 1 and 2 days of colitis (2.2to 3.2-fold, p < 0.05). There were no significant changes in the BDNF protein level in L2 DRG at both days of colitis. In addition, level of ASIC 1a (2.5to 4.3fold, p < 0.05) and 2b (2.7to 3.6-fold, p < 0.05) protein expression in L2 DRG significantly higher after administration. RT PCR results showed significant increases in the level of BDNF mRNA in L1 DRG (2.1to 2.3-fold, p < 0.05) at 1 and 2 days of colitis. ASIC 1a and 2b mRNA expression was significantly increased in L1 level. There was no change in IL-1β and TNF-α expression in colitis group. In butyrate-treated colitis model, administration of DA 9701 led to significantly decreased level of BDNF, ASIC 1a, and ASIC 2b protein and mRNA expression in both L1 and L2 DRG levels compared with control groups. Conclusion: Our data suggest that peripheral BDNF and ASIC1a/2b concomitantly contribute to the development of butyrate-induced colon hypersensitivity. In addition, DA 9701 can negatively modulate the activity of ASICs and BDNF in lumbosacral DRG.