Plasma Levels of Peptide YY Correlate with Cisplatin-induced Emesis in Dogs

Abstract

The effect of cisplatin on plasma peptide YY (PYY) and 5-hydroxytryptamine (5-HT) concentrations was determined in conscious dogs (n = 6 per group) pretreated with either saline, or the 5-HT3-receptor antagonists ondansetron or granisetron. Cisplatin (30 mg kg−1, i.v.) caused emesis (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 concentrations (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 significantly increase (34·7 ± 7·4 vs 35·6 ± 12·3 pM h). The concentrations 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-induced emetic episodes was significantly (P < 0·005) decreased compared with control. In animals receiving cisplatin and pretreated with ondansetron, PYY concentrations were not significantly altered, whereas the 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 cisplatin and pretreated with granisetron, plasma concentrations of 5-HT were not significantly altered, whereas the mean AUC of plasma PYY concentrations 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 concentrations increased significantly (34·7 ± 7·4 to 68·6 ± 37·2 Pm h; P < 0·05) in animals treated with granisetron alone. These studies indicate that plasma concentrations of PYY, and not 5-HT, correlate with cisplatin-induced emesis in dogs. Peptide YY may be an important mediator in cancer chemotherapy-induced emesis and other types of emesis.