Decrease of prolactin secretion via stimulation of pituitary dopamine D-2 receptors after application of talipexole...

The present experiments were performed to investigate the effects of talipexole (B-HT 920) and SND 919 on prolactin release from the anterior pituitary glands of rats both in vivo and in vitro. The basal serum prolactin levels were reduced dose dependently by s.c. administration of talipexole or SND 919 at doses of 5-100 micrograms/kg. Daily treatment with estradiol (35 micrograms/kg for 3 days) increased serum prolactin levels in male rats to levels 4-fold higher than those of non-primed rats. This increase was suppressed by administration of talipexole or SND 919. In vitro, the spontaneous prolactin release into perfusates from isolated anterior pituitary was inhibited by talipexole or SND 919 added at concentrations ranging from 10(-9) to 10(-6) M. This inhibitory effect of SND 919 was blocked by concurrent application of a dopamine D-2 receptor antagonist, YM-09151-2. The spontaneous prolactin release from the anterior pituitary isolated from estradiol-primed rats was 2-fold higher than that from non-primed rats. This increased release was also inhibited by application of either drug. The inhibitory effects of these drugs were greater in estradiol-primed rats than in non-primed rats when expressed as percent inhibition of control prolactin release. The results suggest that talipexole and SND 919 have a selective dopamine D-2 receptor agonistic property and are almost completely effective to counteract the enhancement of prolactin release induced by estrogens via stimulation of dopamine D-2 receptors in the anterior pituitary.