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

Abstract.

Severe nausea and vomiting are common side effects of anti-cancer chemotherapy. 5-HT₃ receptor antagonists have been used for the treatment of these gastrointestinal symptoms. The purpose of this study was to examine whether specific changes in serotonin dynamics occurred in the gastrointestinal tract in mice in which Colon-26 adenocarcinoma cells were injected s.c., especially after treatment with cisplatin. The serotonin content of the small intestine of mice inoculated s.c. with Colon-26 adenocarcinoma increased significantly 2 weeks after the inoculation of the tumor cells; this was associated 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 intestine of Colon-26 tumour-bearing mice but not in control mice. The spontaneous release of serotonin from isolated intestine was not different between Colon-26 tumour-bearing and control mice; however, pretreatment of mice with 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 enterochromaffin 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 may be related to the occurrence of nausea in clinical use.