Department of Neuroscience and Cell Biology, Osaka University Graduate School of Medicine, 2-2, Yamada-oka, Suita, Osaka 565-0871, Japan.
Biochem Biophys Res Commun. 2011 Nov 18;415(2):416-20. doi: 10.1016/j.bbrc.2011.10.084. Epub 2011 Oct 21.
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.
已经表明，抗癌药物会诱导小肠分泌血清素（5-HT），从而激活血清素 3 型（5-HT3）受体，引起恶心和呕吐。通常，5-HT3 受体拮抗剂在化疗期间用作止吐药。然而，我们发现抗癌药物伊立替康本身以浓度依赖的方式抑制同型 5-HT3A 和异型 5-HT3AB 受体的 5-HT 门控电流。伊立替康对 5-HT3A 受体的抑制作用强于对 5-HT3AB 受体的抑制作用。另一方面，伊立替康的代谢物 SN-38 对反应性没有影响。我们的研究结果表明，伊立替康本身可能通过抑制 5-HT3A 和 5-HT3AB 受体发挥止吐作用。
