Inhibitory effect of ramosetron on corticotropin releasing factor- and soybean oil-induced delays in gastric emptying in rats.

Takuya Hirata, Yoshihiro Keto, Mayumi Yamano, Toshihide Yokoyama, Takanori Sengoku, Nobuo Seki

Applied Pharmacology Research Laboratories, Drug Discovery Research, Astellas Pharma Inc., Tsukuba, Ibaraki, Japan. takuya.hirata@astellas.com

Journal of gastroenterology and hepatology 2012 Sep

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Symptoms of functional dyspepsia (FD) are highly prevalent in patients with irritable bowel syndrome (IBS). However, the effects of therapeutic agents for IBS on the pathophysiology of FD are unclear. In this study, therefore, we examined the effects of ramosetron, a serotonin 5-HT(3) receptor antagonist, on corticotropin releasing factor (CRF)- and soybean oil-induced delays in gastric emptying of rats, in comparison with anti-diarrheal agent and spasmolytics. The involvement of 5-HT and the 5-HT(3) receptor in delayed gastric emptying was also evaluated. Corticotropin releasing factor was administered intravenously to rats 10min before oral administration of 0.05% phenol red solution, and the amount remaining in the stomach was measured after 30min. Soybean oil was administered orally with glass beads, and the number of residual beads in the stomach was counted 1h later. Both CRF and soybean oil inhibited gastric emptying dose-dependently. Ramosetron and itopride, a gastro-prokinetic agent, significantly reduced both CRF- and soybean oil-induced delays in gastric emptying, while an anti-diarrheal agent and spasmolytics aggravated them. Pretreatment with p-chlorophenylalanine for 2days to reduced the synthesis of endogenous 5-HT diminished the effects of both CRF and soybean oil on gastric emptying. A 5-HT(3) receptor agonist m-chlorophenylbiguanide suppressed gastric emptying of both phenol red and glass beads, and those effects were reversed by ramosetron. These results suggest that CRF and soybean oil suppress gastric emptying in rats by activating 5-HT(3) receptors, and that by antagonizing these receptors, ramosetron may ameliorate symptoms of FD in clinical settings. © 2012 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd.

Citation

Takuya Hirata, Yoshihiro Keto, Mayumi Yamano, Toshihide Yokoyama, Takanori Sengoku, Nobuo Seki. Inhibitory effect of ramosetron on corticotropin releasing factor- and soybean oil-induced delays in gastric emptying in rats. Journal of gastroenterology and hepatology. 2012 Sep;27(9):1505-11