Plasma levels of peptide YY correlate with cisplatin-induced emesis in dogs.
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 (3.0 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).(ABSTRACT TRUNCATED AT 250 WORDS)
Perry
M R
MR
Department of Gastrointestinal Pharmacology, Syntex Discovery Research, Palo Alto, California 94303.
Rhee
J
J
Smith
W L
WL
D000818:Animals; D002945:Cisplatin / Q000633:toxicity*; D004285:Dogs; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D005260:Female; D017829:Granisetron / Q000494:pharmacology; D007124:Immunoenzyme Techniques; D017294:Ondansetron / Q000494:pharmacology; D019894:Peptide YY; D010455:Peptides / Q000097:blood*; D011863:Radioimmunoassay; D011897:Random Allocation; D012701:Serotonin / Q000097:blood*; D014839:Vomiting / Q000097:blood* / Q000139:chemically induced
D002945:Cisplatin; D017829:Granisetron; D017294:Ondansetron; D019894:Peptide YY; D010455:Peptides; D012701:Serotonin