Various emetogens increase the secretion of salivary amylase in rats: a potential model in emesis research.
We investigated the effects of various emetic agents: cisplatin, apomorphine, lithium chloride (LiCl), rolipram, sibutramine, and the beta(3)-adrenoceptor (AR) agonist CL316243 on salivary amylase secretion in rats. We also determined the inhibitory effect of granisetron, a 5-HT(3)-receptor antagonist, on cisplatin-induced increased salivary amylase activity and the inhibitory effect of bilateral abdominal vagotomy on increases in salivary amylase activity induced by cisplatin and LiCl. Granisetron was administered 15 min before and 1 h after cisplatin administration. Cisplatin (10 - 15 mg/kg, i.v.) increased salivary amylase activity dose-dependently and induced an acute increase from 1.5 h post-treatment with 15 mg/kg. Apomorphine (1 - 3 mg/kg, s.c.), LiCl (120 mg/kg, i.p.), rolipram (3 - 10 mg/kg, p.o.), and sibutramine (10 mg/kg, p.o.) induced significant increases in salivary amylase secretion. On the other hand, CL316243 did not stimulate salivary amylase secretion. The increased amylase activity induced by cisplatin (15 mg/kg, i.v.) was inhibited significantly by granisetron (1 or 3 mg/kg x 2, i.v.) or tended to be inhibited by bilateral abdominal vagotomy, whereas an increase in amylase activity produced by LiCl was not inhibited by abdominal visceral nerve section. These results suggest that salivary amylase activity is useful as a marker for emesis in rats, a species that does not exhibit vomiting.
Fukui
Hideo
H
Development Research Center, Takeda Pharmaceutical Company, Ltd., Osaka, Japan. Fukui_Hideo@takeda.co.jp
Miwa
Eri
E
Iwachido
Takako
T
Kitaura
Harumi
H
Furukawa
Hatsue
H
D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000681:Amylases / Q000378:metabolism*; D000818:Animals; D001058:Apomorphine / Q000494:pharmacology*; D002945:Cisplatin / Q000494:pharmacology*; D003503:Cyclobutanes / Q000494:pharmacology; D003864:Depression, Chemical; D004149:Dioxoles / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004639:Emetics / Q000494:pharmacology*; D017829:Granisetron / Q000494:pharmacology*; D018021:Lithium Chloride / Q000494:pharmacology*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D020889:Rolipram / Q000494:pharmacology; D012463:Saliva / Q000201:enzymology*; D012702:Serotonin Antagonists / Q000494:pharmacology*; D013268:Stimulation, Chemical; D014628:Vagotomy
D000318:Adrenergic beta-Agonists; D000681:Amylases; D001058:Apomorphine; D002945:Cisplatin; D003503:Cyclobutanes; D004149:Dioxoles; D004639:Emetics; D017829:Granisetron; D018021:Lithium Chloride; D020889:Rolipram; D012702:Serotonin Antagonists; C076126:disodium (R,R)-5-(2-((2-(3-chlorophenyl)-2-hydroxyethyl)-amino)propyl)-1,3-benzodioxole-2,3-dicarboxylate; C058254:sibutramine