Anticancer drug irinotecan inhibits homomeric 5-HT_3A and heteromeric 5-HT_3AB receptor responses

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• 作者：Yukiko  ; Nakamura  ; ;   ; ^{ynakamura@anat1.med.osaka-u.ac.jp} ; Yusuke  ; Ishida ;   ; ^{ishida@anat1.med.osaka-u.ac.jp} ; Takahiro  ; Yamada ;   ; ^{yamada@anat1.med.osaka-u.ac.jp} ; Shoichi  ; Shimada ;   ; ^{shimada@anat1.med.osaka-u.ac.jp}
• 关键词：5-HT ; 5-HT₃ receptor ; Ion channel ; Vagus nerve ; Anti-emetic ; Anti-cancer
• 刊名：Biochemical and Biophysical Research Communications
• 出版年：2011
• 出版时间：18 November 2011
• 年：2011
• 卷：415
• 期：2
• 页码：416-420
• 全文大小：468 K

文摘

It has been shown that anti-cancer drug induces secretion of serotonin (5-HT) from small intestine which activates serotonin type 3 (5-HT₃) receptor to cause nausea and vomiting. In general, antagonist for 5-HT₃ 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.