title: Anticancer drug irinotecan inhibits homomeric 5-HT3A and heteromeric 5-HT3AB receptor responses.
abstract: It has been shown that anti-cancer drug induces secretion of serotonin (5-HT) from small intestine which activates serotonin type 3 (5-HT(3)) receptor to cause nausea and vomiting. In general, antagonist for 5-HT(3) receptor is used as anti-emetics during chemotherapy. However, we found that anti-cancer drug irinotecan itself inhibits 5-HT-gated current through the homomeric 5-HT(3A) and heteromeric 5-HT(3AB) receptor in a concentration-dependent manner. The inhibitory effect of irinotecan on 5-HT(3A) receptor was more potent than that on 5-HT(3AB) receptor. On the other hand, SN-38, a metabolite of irinotecan, had no effect on the responsiveness. Our findings suggest that irinotecan itself could have anti-emetic activities through inhibition of the 5-HT(3A) and 5-HT(3AB) receptor.
authors: Department of Neuroscience and Cell Biology, Osaka University Graduate School of Medicine, 2-2, Yamada-oka, Suita, Osaka 565-0871, Japan. ynakamura@anat1.med.osaka-u.ac.jp
authors: Yukiko
authors: Y
authors: Nakamura
authors: Yusuke
authors: Y
authors: Ishida
authors: Takahiro
authors: T
authors: Yamada
authors: Shoichi
authors: S
authors: Shimada
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000494:pharmacology; D006801:Humans; D000077146:Irinotecan; D044406:Receptors, Serotonin, 5-HT3 / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism; D058831:Serotonin 5-HT3 Receptor Antagonists / Q000494:pharmacology*; D014982:Xenopus laevis
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D044406:Receptors, Serotonin, 5-HT3; D058831:Serotonin 5-HT3 Receptor Antagonists; D012701:Serotonin; D000077146:Irinotecan; D002166:Camptothecin