Suppression of prolactin release and mRNA accumulation by two novel dopamine agonist agents

Two novel dopamine agonist drugs, CV 205-502 and CQP 201-403, have been investigated to compare their effects on prolactin secretion and prolactin mRNA accumulation in cultured rat pituitary cells. Both drugs gave dose-dependent suppression of prolactin release over a 24 h incubation period: when each drug was used at 100 nmol/l CV 205-502 and CQP 201-403 induced suppression to 8.9 +/- 1.7 and 10.2 +/- 1.8% of control release, respectively, compared to 26.7 +/- 4.8% of control with 100 nmol/l bromocriptine. There was no consistent effect on growth hormone release. Cytoplasmic accumulation of prolactin mRNA was also inhibited by both drugs at this concentration, to 50.2 +/- 5.5% of control values by CV 205-502 and to 67.4 +/- 8% of control by CQP 201-403, and to a similar extent by 100 nmol/l bromocriptine (50.6 +/- 9.1% of control). None of the drugs had any significant effect on GH mRNA levels. These data suggest that the agents exert their effect at a pretranslational stage of prolactin synthesis, as well as at the level of hormone release.