Chemical modulation of 5-HT3 and 5-HT4 receptors affects the release of 5-hydroxytryptamine from the ferret and rat intestine
Minami, M.; Tamakai, H.; Ogawa, T.; Endo, T.; Hamaue, N.; Hirafuji, M.; Yoshioka, M.; Blower, P.R.
Research Communications in Molecular Pathology and Pharmacology 89(2): 131-142
1995
ISSN/ISBN: 1078-0297 PMID: 8556268 Document Number: 869
In species which vomit, elevated intestinal serotonin (5-hydroxytryptamine, 5-HT) may stimulate abdominal vagal afferent fibers, which in turn evoke the vomiting reflex. The release of 5-HT from intestinal enterochromaffin (EC) cells is regulated by polymodal mechanisms. The object of this study was to evaluate the involvement of 5-HT autoreceptors in the regulation of 5-HT release from the small intestine. Functional studies were carried out using 5-HT-3 receptor agonist and antagonists, and 5-HT-4 receptor agonist. Ferret and rat ileal tissue were isolated and 5-HT released into the bathing solution was determined using HPLC with an electrochemical detector (ECD). We previously reported that cisplatin produced a significant increase in cumulative 5-HT release and that ondansetron, a selective 5-HT-3 receptor antagonist, did not alter the 5-HT release from the ferret ileum. In this study, a selective 5-HT-3 agonist, 2-methyl-5-HT, induced a dose-dependent increase of 5-HT from the rat ileum. This release of 5-HT was significantly reduced by granisetron, a selective 5-HT-3 receptor antagonist. Furthermore, a selective 5-HT-4 receptor agonist, 5-methoxytryptamine induced a concentration-dependent increase of 5-HT in the rat ileum. These results suggest that both 5-HT-3 and 5-HT-4 receptors may be involved in intestinal 5-HT release.
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