EFFECTS OF ANTICANCER DRUGS ON ENZYME-ACTIVITIES AND SEROTONIN RELEASE FROM ILEAL TISSUE IN FERRETS

We previously reported that intestinal serotonin (5-HT) concentrations in the cisplatin- and copper sulfate-treated groups increased signifi cantly as compared with the control group. Elevated intestinal 5-HT ma y stimulate the 5-HT3 receptors on the afferent vagal fibers. Stimulat ion of these 5-HT3 receptors would induce abnormal discharges of the v agal fibers which evoke the vomiting reflex. In order to elucidate the mechanism of 5-HT increase induced by anticancer drugs, biosynthetic and metabolic enzyme activities of ileal 5-HT using ferret were measur ed. Ileal 5-HT release was also determined. Tryptophan hydroxylase (TP H) activity in anticancer drug-treated groups increased significantly. Ileal aromatic L-amino acid decarboxylase (AADC) activity of the emet ic drug-treated groups increased significantly, and ileal monoamine ox idase (MAO) activity decreased significantly as compared with control groups. Pretreatment of ondansetron and vagotomy did not influence the changes of these enzyme activities induced by cisplatin. Ileal releas e of 5-HT after cisplatin administration produced a significant increa se as compared with the control group. These findings suggest that ant icancer drugs such as cisplatin and cyclophosphamide, and copper sulfa te stimulate the release and biosynthesis of 5-HT from the ileum which directly sensitized gastrointestinal vagal afferent axons.