title: Differential effects of talipexole and bromocriptine on serotonin release from rat intestinal tissues--an in vitro study of the emetic response of antiparkinsonian dopamine agonists.
abstract: In order to elucidate the role of emetic action, the effects of talipexole and bromocriptine, two antiparkinsonian dopamine receptor agonists, on serotonin (5-HT) release from enterochromaffin (EC) cells were studied by measuring 5-HT concentrations in the perfusate of the isolated rat ileum. Bromocriptine (10(-8)-10(-6) M), which exerts agonistic effects on D1 and D2 receptors, increased 5-HT release in a concentration-dependent manner. No significant increase in 5-HT release was seen after addition of talipexole, which selectively stimulates D2 receptors and blocks 5-HT3 receptors, even at 10(-6) M. The increase in 5-HT release caused by bromocriptine at 10(-6) M was inhibited by administration of 10(-6) M of D1 receptor antagonist SCH 23390, D2 receptor antagonist spiperone, 5-HT3 receptor antagonist granisetron or tetrodotoxin (TTX). These results showed the involvement of both dopaminergic and serotonergic mechanisms in the 5-HT release from EC cells following the administration of dopamine receptor agonists. Bromocriptine might induce 5-HT release by stimulating D1, D2 and 5-HT3 receptors and depolarizing neurons in the ileum. On the other hand, talipexole might weaken 5-HT release from EC cells elicited by D2 receptor stimulation with its 5-HT3 receptor blocking property. It is suggested that the emetic effect of dopamine receptor agonists involves the peripheral gastrointestinal tract as their site of action.
authors.affiliation: Department of Pharmacology, Faculty of Pharmaceutical Sciences, Health Science University of Hokkaido, Ishikari-Tobetsu, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Minami
authors.forename: Y
authors.initials: Y
authors.lastname: Kohno
authors.forename: T
authors.initials: T
authors.lastname: Endo
authors.forename: M
authors.initials: M
authors.lastname: Nemoto
authors.forename: T
authors.initials: T
authors.lastname: Ogawa
authors.forename: E
authors.initials: E
authors.lastname: Ihira
authors.forename: N
authors.initials: N
authors.lastname: Hamaue
authors.forename: M
authors.initials: M
authors.lastname: Hirafuji
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001381:Azepines / Q000008:administration & dosage / Q000494:pharmacology*; D001971:Bromocriptine / Q000008:administration & dosage / Q000494:pharmacology*; D018491:Dopamine Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D007082:Ileum / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000378:metabolism*
chemical_list: D001381:Azepines; D018491:Dopamine Agonists; D012701:Serotonin; D001971:Bromocriptine; C024763:talipexole