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  • Title: Effects of various 5-HT3 receptor antagonists, granisetron, ondansetron, ramosetron and azasetron on serotonin (5-HT) release from the ferret isolated ileum.
    Author: Endo T, Minami M, Kitamura N, Teramoto Y, Ogawa T, Nemoto M, Hamaue N, Hirafuji M, Yasuda E, Blower PR.
    Journal: Res Commun Mol Pathol Pharmacol; 1999; 104(2):145-55. PubMed ID: 10634307.
    Abstract:
    The object of this study was to evaluate the involvement of 5-HT3 receptors in the regulation of 5-HT release from the small intestine using ferrets, an animal model of emesis. 2-Methyl-5-HT, a 5-HT3 receptor agonist, produced a concentration-dependent increase of 5-HT from the ferret ileum. This increase in 5-HT release was significantly inhibited by granisetron (10(-7) and 10(-6) M) or azasetron (10(-7) and 10(-6) M) in a concentration-dependent manner. Ondansetron (10(-7) M) and ramosetron (10(-6) M) also significantly inhibited the 2-methyl-5-HT-induced increase in 5-HT release. When the concentration of ondansetron was increased from 10(-7) M to 10(-6) M, inhibition of 5-HT release was reduced. Ramosetron, for which 5-HT3 receptor binding of the rat brain is remarkably stronger than for any other 5-HT3 receptor antagonists, inhibited the 5-HT release at only the highest concentration of 10(-6) M. Based on these observations that the mode of action on the 2-methyl-5-HT induced 5-HT release is different among 5-HT3 receptor antagonists, it is suggested that there is a possibility that the neuronal 5-HT3 receptors and the 5-HT3 receptors on the EC cells may represent two distinct subtypes.
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