Dopamine D2 receptor mediates both inhibitory and stimulatory actions on prolactin release

Dopamine is considered to be the major physiological tonic inhibitor of prolactin release, yet there is increasing evidence showing that it can also stimulate prolactin release from lactotrophs. In primary cultured lactotrophs, the major dopamine receptors responsible for inhibiting prolactin release are dopamine D-2 receptors. A dopamine receptor subtype may be responsible for the stimulatory action, yet one cannot exclude the possibility that a dopamine D, receptor can play dual roles. This study was therefore undertaken to investigate if dopamine both stimulates and inhibits prolactin secretion through activation of the same dopamine D-2 receptor, GH(4)ZR(7) cells, which have only one type of dopamine receptors-D-2s, were perifused with different concentrations of dopamine, and the perifusate was assayed for prolactin; 10(-7) mol/L dopamine stimulated prolactin release (p < 0.05; n = 5), whereas 5 x 10(-4) mol/L dopamine inhibited prolactin secretion (p < 0.05; n = 5). In the pertussis toxin-treated cells, 10(-7) mol/L dopamine stimulated prolactin release (p < 0.05; n = 5), and 5 x 10(-4) mol/L dopamine did not significantly change the rate of prolactin release. These results indicate that both the stimulatory and inhibitory actions of dopamine are likely mediated by the same D-2 receptor subtype, since GH(4)ZR(7) cells express only D-2s receptors. They also confirm that the inhibitory action of dopamine is mediated through a G(i) protein; and the stimulatory action of dopamine is mediated through a PTX-insensitive pathway. These findings suggest that D-2 receptors are coupled to both G(i) and G(s) proteins.