Differential Inhibition of Dopamine and Bromocriptine on Induced Prolactin Release: Multiple Sites for the Inhibition of Dopamine

Abstract

Effects of dopamine and bromocriptine on TRH- or dibutyryladenosine 3’,5’-cyclic monophosphate (dbcAMP)-induced prolactin release from primary cultured rat pituitary cells were studied using a perifusion system. TRH (100 nmol/l) stimulated prolactin release from basal concentrations of 33.8 ± 0.5 to 151.2 ± 28.0 ng/ml (net increase) or 447% increase. Dopamine inhibited the basal release of prolactin throughout the experiment, but TRH (100 nmol/l) was still able to stimulate prolactin release under the influence of dopamine. The increment in prolactin release was inversely proportional to the dopamine concentration. When TRH (100 nmol/l) was introduced during a perifusion period with bromocriptine 1 nmol/l, the prolactin concentration was increased to 110.9% of basal levels. The stimulatory effect of TRH under the influence of bromocriptine (1 nmol/l) was significantly lower than that without bromocriptine (control), although the higher concentrations of bromocriptine (10 and 100 nmol/l) did not further reduce the peak concentration of TRH-induced prolactin release. During a perifusion period with a low concentration of dopamine (1 nmol/l plus 0.1 mmol/l ascorbic acid), introduction of dbcAMP (3 mmol/l) stimulated prolactin release to 48% of basal concentration. A higher concentration of dopamine further reduced the stimulatory effect of prolactin release. Bromocriptine impeded the stimulatory effect of dbcAMP (3 mmol/l) on prolactin release in a similar manner as dopamine. Since a higher concentration of bromocriptine (10 and 100 nmol/ 1) did not further inhibit the TRH-induced prolactin release whereas a higher concentration of dopamine did, it is concluded that dopamine acts through additional mechanism(s) other than the D₂ receptor transduction system.

Dopamine agonists both stimulate and inhibit prolactin release in GH4ZR7 cells

“…These dopaminergic agonists inhibit prolactin release but their inhibitory characteristics are very different (36). All three dopaminergic agonists have stimulatory as well as inhibitory actions on prolactin release in GH 4 ZR 7 cells, but their potencies regarding the stimulatory action are different.…”

“…¹8 mol/l DA in primary cultured rat pituitary cells (36), but it is inhibited by about 10 ¹4 mol/l DA in GH 4 ZR 7 cells, indicating that GH 4 ZR 7 cells are much less sensitive to DA than primary cultured lactotrophs. The difference in the potencies is probably due to different numbers of active D 2 receptors (10).…”

“…Dopamine, apomorphine and bromocriptine produced their peak stimulatory effects at 10 ¹8 , 10 ¹10 and 10 ¹6 mol/l respectively. Regarding the inhibitory actions of the three DA agonists, on the other hand, our laboratory previously demonstrated that bromocriptine inhibited prolactin synthesis and release more potently than DA in primary cultured rat pituitary cells (36,37), and Denef et al (14) demonstrated earlier that apomorphine is more potent than DA in suppressing prolactin release in primary rat pituitary cultures. However, in this study we observed that their peak inhibitory actions were at similar concentrations, between 10 ¹4 and 10 ¹3 mol/l.…”

“…In addition, the patterns of prolactin release induced by these agonists and antagonists can also be different. For example, both DA and bromocriptine inhibit prolactin release via activating dopamine D 2 receptors, yet only withdrawal of DA infusion, but not withdrawal of bromocriptine infusion, causes rebounding of prolactin release over the basal rate in a perifusion system of primary cultured rat pituitary cells (36). Both pimozide and d-butaclamol are well-established D 2 receptor antagonists, but temporal patterns of prolactin release in male rats after injection of pimozide or d-butaclamol are substantially different (39).…”

Divergent prolactin and pituitary-adrenal activity in rats selectively bred for different dopamine responsiveness.

“…For instance, stress induces a PRL response, and this release of PRL is under inhibitory control of dopa mine (1)(2)(3). Furthermore, rats with a predisposition to de velop amphetamine self-administration display prolonged adrenocortical activation and increased locomotor activity after exposure to the stress of novel environment (4)(5)(6).…”