Serotonin-independent model of cisplatin-induced emesis in the ferret.
para-Chlorophenylalanine (PCPA, 100-200 mg/kg) was used as a pharmacological tool to characterize the 5-hydroxytryptamine (5-HT) involvement in the emesis occurring 24 hr after the administration of cisplatin (10 mg/kg) in the ferret. PCPA was effective to antagonize the initial 8 hr period of retching and vomiting, but potentiated the emesis that occurred during the remaining 8- to 24-hr observation period. Tissue samples removed from the brainstem at 24 hr post injection of cisplatin alone revealed an elevation of 5-HT, dopamine and homovanillic acid that was antagonized by the injection of PCPA. Cisplatin also induced increases in the urinary levels of 5-hydroxyindoleacetic acid that was similarly antagonized by PCPA. Results are discussed in terms of the relevance of 5-HT to the model of cisplatin (10 mg/kg)-induced emesis in the ferret compared to the problem of acute and delayed emesis in man. The residual or delayed phase of cisplatin-induced emesis may involve a 5-HT-independent mechanism.
Rudd
J A
JA
Department of Pharmacology, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, NT.
Cheng
C H
CH
Naylor
R J
RJ
D006916:5-Hydroxytryptophan / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002945:Cisplatin / Q000009:adverse effects* / Q000494:pharmacology; D003432:Cross-Linking Reagents / Q000009:adverse effects* / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism; D004837:Epinephrine / Q000378:metabolism; D010134:Fenclonine / Q000494:pharmacology; D005289:Ferrets / Q000378:metabolism*; D006719:Homovanillic Acid / Q000378:metabolism; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D007082:Ileum / Q000187:drug effects / Q000378:metabolism; D008297:Male; D011136:Polysorbates / Q000494:pharmacology; D012701:Serotonin / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000494:pharmacology; D014839:Vomiting / Q000139:chemically induced*
D003432:Cross-Linking Reagents; D011136:Polysorbates; D012702:Serotonin Antagonists; D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; D006916:5-Hydroxytryptophan; D002945:Cisplatin; D010134:Fenclonine; D004298:Dopamine; D006719:Homovanillic Acid; D004837:Epinephrine