INCREASE IN SEROTONIN LEVELS IN THE DOG ILEUM AND BLOOD BY CISPLATIN AS MEASURED BY MICRODIALYSIS

被引:51
作者
FUKUI, H [1 ]
YAMAMOTO, M [1 ]
ANDO, T [1 ]
SASAKI, S [1 ]
SATO, S [1 ]
机构
[1] TAKEDA CHEM IND LTD,DIV PHARMACEUT DEV,DRUG SAFETY RES LABS,6-10-1 HIMURO CHO,TAKATSUKI,OSAKA 569,JAPAN
关键词
CISPLATIN; DOG; MICRODIALYSIS; 5-HT; ENTEROCHROMAFFIN CELLS; VOMITING;
D O I
10.1016/0028-3908(93)90060-G
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Involvement of ileal and circulating serotonin (5-HT) levels in cisplatin-induced emesis was examined using a microdialysis technique and an extraction method in dogs. The 5-HT levels in the ileal dialysate were increased to 232-294% of the basal level from 100 to 180 min after cisplatin administration (3 mg/kg, i.v.) and had returned to the basal level 280 min after dosing. The 5-HT levels in the blood dialysate were increased to 424-2165% from 140 to 180 min after dosing. The concentrations of 5-HT determined by HPLC following extraction were increased to 271% in the ileal mucosa and to 478% in plasma 3 hr after dosing. In immunohistochemistry, the number of 5-HT-immunoreactive cells was increased to 166% in the ileal mucosa following cisplatin treatment. These results strongly suggest that increases in the release and synthesis of 5-HT in the gut, probably in the enterochromaffin cells, are intimately involved in cisplatin-induced emesis.
引用
收藏
页码:959 / 968
页数:10
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