Increase in serotonin levels in the dog ileum and blood by cisplatin as measured by microdialysis.
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.
Fukui
H
H
Drug Safety Research Laboratories, Takeda Chemical Industries Ltd., Osaka, Japan.
Yamamoto
M
M
Ando
T
T
Sasaki
S
S
Sato
S
S
D000818:Animals; D002945:Cisplatin / Q000494:pharmacology* / Q000633:toxicity; D004285:Dogs; D004759:Enterochromaffin Cells / Q000187:drug effects; D005260:Female; D007082:Ileum / Q000187:drug effects / Q000378:metabolism*; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism; D008297:Male; D017551:Microdialysis; D012701:Serotonin / Q000097:blood / Q000378:metabolism*; D014839:Vomiting / Q000139:chemically induced / Q000378:metabolism
D012701:Serotonin; D002945:Cisplatin