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.
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.
Minami
M
M
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Health Science University of Hokkaido, Ishikari-Tobetsu, Japan.
Kohno
Y
Y
Endo
T
T
Nemoto
M
M
Ogawa
T
T
Ihira
E
E
Hamaue
N
N
Hirafuji
M
M
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*
D001381:Azepines; D018491:Dopamine Agonists; D012701:Serotonin; D001971:Bromocriptine; C024763:talipexole