title: Effects of fluvoxamine, a selective serotonin re-uptake inhibitor, on serotonin release from the mouse isolated ileum.
abstract: The presence of nausea and vomiting is problematic for all selective serotonin re-uptake inhibitors (SSRIs), and their usefulness as anti-depressants is limited in this respect. In an attempt to examine the background of SSRI-induced emesis, the present study aims to describe the role of 5-hydroxytryptamine (serotonin:5-HT) from the viewpoint of 5-HT release in the mouse-isolated ileum. In this study, it was demonstrated that 5-HT release from the mouse-isolated ileum was significantly increased by fluvoxamine at a concentration of 10(-6) M. Also, it was demonstrated that granisetron, a 5-HT3 receptor antagonist, inhibited significantly the increase in fluvoxamine (10(-6) M) -induced 5-HT release. The effect of granisetron on fluvoxamine-induced 5-HT release was occurred in a concentration-dependent manner. The present study demonstrated for the first time that the SSRI-induced increase in 5-HT release from the isolated ileum was significantly inhibited by 5-HT3 receptor antagonist. These results suggest that 5-HT3 receptors might be involved in SSRI-induced 5-HT release from the mouse isolated ileal tissue. Fluvoxamine (10(-6) M)-induced 5-HT release was inhibited concentration -dependently by the concomitant perfusion of diltiazem. The results suggest that L-type calcium channel might be also involved in SSRI-induced 5-HT release from the isolated ileum. Furthermore, tetrodotoxin (10(-6) M) completely inhibited the increase in 5-HT release induced by fluvoxamine. This finding suggests that the increase of 5-HT induced by fluvoxamine involves enterochromaffin (EC) cell stimulation via an inter-neuron pathway in the gastrointestinal tract (GI). SSRI initiates an increase in the concentration of 5-HT in the GI tract. 5-HT released from the EC cells of the intestinal mucosa may stimulate the 5-HT3 receptors on vagal afferent nerve fibers. This depolarization of vagal afferents may result in a 5-HT increase in the brainstem and, thus, lead to emesis.
authors.affiliation: Department of Pharmacology, Health Sciences University of Hokkaido, Ishikari-Tobetsu, Hokkaido 061-0293, Japan. minami@hoku-iryo-u.ac.jp
authors.forename: Masaru
authors.initials: M
authors.lastname: Minami
authors.forename: Shin
authors.initials: S
authors.lastname: Taguchi
authors.forename: Takuro
authors.initials: T
authors.lastname: Kikuchi
authors.forename: Toru
authors.initials: T
authors.lastname: Endo
authors.forename: Naoya
authors.initials: N
authors.lastname: Hamaue
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Hiroshige
authors.forename: Yanxia
authors.initials: Y
authors.lastname: Liu
authors.forename: Wang
authors.initials: W
authors.lastname: Yue
authors.forename: Masahiko
authors.initials: M
authors.lastname: Hirafuji
mesh_terms: D000818:Animals; D000932:Antiemetics / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D004110:Diltiazem / Q000494:pharmacology; D004347:Drug Interactions; D016666:Fluvoxamine / Q000633:toxicity*; D017829:Granisetron / Q000494:pharmacology; D007082:Ileum / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D012701:Serotonin / Q000378:metabolism*; D017367:Selective Serotonin Reuptake Inhibitors / Q000633:toxicity*; D014839:Vomiting / Q000139:chemically induced
chemical_list: D000932:Antiemetics; D002121:Calcium Channel Blockers; D004110:Diltiazem; D016666:Fluvoxamine; D017829:Granisetron; D012701:Serotonin; D017367:Selective Serotonin Reuptake Inhibitors