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 D2 receptors. A dopamine receptor subtype may be responsible for the stimulatory action, yet one cannot exclude the possibility that a dopamine D2 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 D2 receptor. GH4ZR7 cells, which have only one type of dopamine receptors--D2s, 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 D2 receptor subtype, since GH4ZR7 cells express only D2s receptors. They also confirm that the inhibitory action of dopamine is mediated through a Gi protein; and the stimulatory action of dopamine is mediated through a PTX-insensitive pathway. These findings suggest that D2 receptors are coupled to both Gi and Gs proteins.
Chang
A
A
Department of Physiology, Queen's University, Kingston, Ontario, Canada.
Shin
S H
SH
Pang
S C
SC
D000818:Animals; D002460:Cell Line; D004298:Dopamine / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000502:physiology; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000502:physiology; D007700:Kinetics; D037342:Pertussis Toxin; D010911:Pituitary Neoplasms; D011388:Prolactin / Q000378:metabolism*; D051381:Rats; D017448:Receptors, Dopamine D2 / Q000235:genetics / Q000502:physiology*; D014162:Transfection; D014407:Tumor Cells, Cultured; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D017448:Receptors, Dopamine D2; D010566:Virulence Factors, Bordetella; D011388:Prolactin; D037342:Pertussis Toxin; D019206:GTP-Binding Protein alpha Subunits, Gi-Go; D019205:GTP-Binding Protein alpha Subunits, Gs; D004298:Dopamine