Changes in serotonin dynamics in the gastrointestinal tract of Colon-26 tumour-bearing mice: effects of cisplatin treatment

Severe nausea and vomiting are common side effects of anti-cancer chemother apy. 5-HT3 receptor antagonists have been used for the treatment of these g astrointestinal symptoms. The purpose of this study was to examine whether specific changes in serotonin dynamics occurred in the gastrointestinal tra ct in mice in which Colon-26 adenocarcinoma cells were injected s.c., espec ially after treatment with cisplatin. The serotonin content of the small in testine of mice inoculated s.c. with Colon-26 adenocarcinoma increased sign ificantly 2 weeks after the inoculation of the tumor cells; this was associ ated with an increase in tryptophan hydroxylase activity and the number of enterochromaffin cells as compared with control mice. Intravenous injection of cisplatin significantly reduced the serotonin content in the small inte stine of Colon-26 tumour-bearing mice but not in control mice. The spontane ous release of serotonin from isolated intestine was not different between Colon-26 tumour-bearing and control mice; however, pretreatment of mice wit h cisplatin induced two fold increases in serotonin release from duodenum, jejunum and ileum in Colon-26 tumour-bearing mice but not in control mice. These results indicate that a region-specific increase in the number of ent erochromaffin cells is observed in the intestine of Colon-26 tumour-bearing mice, associated with an increase in the serotonin content and tryptophan hydroxylase activity. Cisplatin treatment induced the release of serotonin from affected enterochromaffin cells in the gastrointestinal tract, which m ay be related to the occurrence of nausea in clinical use.