Chemical modulation of 5-HT3 and 5-HT4 receptors affects the release of 5-hydroxytryptamine from the ferret and rat intestine.
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-HT3 receptor agonist and antagonists, and 5-HT4 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-HT3 receptor antagonist, did not alter the 5-HT release from the ferret ileum. In this study, a selective 5-HT3 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-HT3 receptor antagonist. Furthermore, a selective 5-HT4 receptor agonist, 5-methoxytryptamine induced a concentration-dependent increase of 5-HT in the rat ileum. These results suggest that both 5-HT3 and 5-HT4 receptors may be involved in intestinal 5-HT release.
Minami
M
M
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Health Sciences University of Hokkaido, Japan.
Tamakai
H
H
Ogawa
T
T
Endo
T
T
Hamaue
N
N
Hirafuji
M
M
Yoshioka
M
M
Blower
P R
PR
D008735:5-Methoxytryptamine / Q000494:pharmacology; D000818:Animals; D005289:Ferrets; D017829:Granisetron / Q000494:pharmacology; D007082:Ileum / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D066298:In Vitro Techniques; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D011985:Receptors, Serotonin / Q000145:classification / Q000187:drug effects* / Q000502:physiology*; D012701:Serotonin / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology
D008735:5-Methoxytryptamine; D017829:Granisetron; D011985:Receptors, Serotonin; D012701:Serotonin; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; C045918:2-methyl-5-HT