PLASMA-LEVELS OF PEPTIDE YY CORRELATE WITH CISPLATIN-INDUCED EMESIS IN DOGS

The effect of cisplatin on plasma peptide YY (PW) and 5-hydroxytryptam ine (5-HT) concentrations was determined in conscious dogs (n = 6 per group) pretreated with either saline, or the 5-HT3-receptor antagonist s ondansetron or granisetron. Cisplatin (3.0 mg kg(-1), i.v.) caused e mesis (18.8 +/- 2.9 episodes; 75-284 min) and significantly increased the mean area under the curve (AUC) over a 6-h period of plasma PYY co ncentrations (7.4 +/- 1.8 to 11.5 +/- 3.7 ng) in all saline-pretreated dogs, whereas the mean AUC of plasma 5-HT concentrations did not sign ificantly increase (34.7 +/- 7.4 vs 35.6 +/- 12.3 pM h). The concentra tions of PYY correlated closely with the incidence of emesis (r = 0.99 ). In animals pretreated (36 min) with ondansetron (0.316 mg kg(-1), i .v.) or granisetron (0.316 mg kg(-1), i.v.), the number of cisplatin-i nduced emetic episodes was significantly (P < 0.005) decreased compare d with control. In animals receiving cisplatin and pretreated with ond ansetron, PYY concentrations were not significantly altered, whereas t he mean AUC of plasma concentrations of 5-HT over 6 h increased (35.6 +/- 12.3 to 82.3 +/- 34.6 pM h; P < 0.05). In animals receiving cispla tin and pretreated with granisetron, plasma concentrations of 5-HT wer e not significantly altered, whereas the mean AUC of plasma PYY concen trations were significantly reduced compared with control (6.2 +/- 1.7 vs 11.5 +/- 3.7 ng h). Furthermore, in animals receiving ondansetron without cisplatin treatment, there was no change in the mean AUC of 5- HT or PYY concentrations, whereas the mean AUC of plasma 5-HT concentr ations increased significantly (34.7 +/- 7.4 to 68.6 +/- 37.2 pM h; P < 0.05) in animals treated with granisetron alone. These studies indic ate that plasma concentrations of PYY, and not 5-HT, correlate with ci splatin-induced emesis in dogs. Peptide YY may be an important mediato r in cancer chemotherapy-induced emesis and other types of emesis.