Minami M, Kohno Y, Endo T, Nemoto M, Ogawa T, Ihira E, Hamaue N, Hirafuji M
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Health Science University of Hokkaido, Ishikari-Tobetsu, Japan.
Res Commun Mol Pathol Pharmacol. 1999;104(1):3-12.
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.
