Mechanisms of cisplatin- and m-chlorophenylbiguanide-induced emesis in ferrets.
We investigated the involvement of peripheral and central serotonin (5-HT)3 receptors in cisplatin- and 5-HT3 receptor agonist-induced emesis in ferrets. Cisplatin (10 mg/kg i.v.)-induced emesis was inhibited by intravenous YM060 (0.003-0.1 microgram/kg). A highly selective and potent 5-HT3 receptor agonist, m-chlorophenylbiguanide (1-10 mg/kg i.p.), dose dependently elicited emesis an effect which was inhibited by YM060 (0.003-0.3 microgram/kg i.v.). Vagotomy markedly reduced this emesis, and the combination of abdominal vagotomy and greater splanchnicectomy abolished emesis. Lesion of greater splanchnic nerves alone did not markedly inhibit emesis. Intracerebroventricularly (4th ventricle) administered YM060 inhibited cisplatin- and m-chlorophenylbiguanide-induced emesis only at higher doses (0.01-0.1 and 0.01-0.03 microgram, respectively). Intracerebroventricularly (4th ventricle) administered m-chlorophenylbiguanide (30-100 micrograms) produced only a weak retching response. These results indicate that stimulation of abdominal vagal afferent nerves via peripheral 5-HT3 receptors is important for triggering cisplatin- and m-chlorophenylbiguanide-induced emesis in ferrets.
Kamato
T
T
Neuroscience Research Laboratory, Yamanouchi Pharmaceutical Co. Ltd., Ibaraki, Japan.
Ito
H
H
Nagakura
Y
Y
Nishida
A
A
Yuki
H
H
Yamano
M
M
Miyata
K
K
D000818:Animals; D001562:Benzimidazoles / Q000008:administration & dosage / Q000494:pharmacology; D001645:Biguanides / Q000494:pharmacology*; D002945:Cisplatin / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005289:Ferrets; D007275:Injections, Intravenous; D007276:Injections, Intraventricular; D008297:Male; D011985:Receptors, Serotonin / Q000187:drug effects* / Q000378:metabolism; D012702:Serotonin Antagonists; D013153:Splanchnic Nerves / Q000502:physiology / Q000601:surgery; D014628:Vagotomy; D014630:Vagus Nerve / Q000502:physiology; D014839:Vomiting / Q000139:chemically induced*
D001562:Benzimidazoles; D001645:Biguanides; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; C071315:ramosetron; C065734:1-(3-chlorophenyl)biguanide; D002945:Cisplatin