D2-dopamine agonists inhibit adenosine 3':5'-cyclic monophosphate (cAMP) production in human term trophoblastic cells

We previously reported that dopamine (DA) acted via D2-dopamine receptors on human trophoblastic cells to inhibit basal and hormone-stimulated secretion of human placental lactogen (hPL). We also described that these DA effects were coupled with inhibition of calcium influx. The present study examines the interaction of placental D2-dopamine receptor with adenylate cyclase (AC). Incubations of isolated human term trophoblastic cells with R(-)-propylapomorphine (NPA), (+/-)-PPHT, and bromocriptine (3 different D2 agonists) led to time- and dose-dependent inhibitions of cAMP production as determined by measuring the conversion of [2-3H]-ATP into [2-3H]-cAMP. The maximal inhibition was reached after 15 min of incubation and was 33 +/- 1 (SE) %, 29 +/- 3% and 31 +/- 1% for bromocriptine (10(-5) M), NPA (10(-7) M) and (+/-)-PPHT (10(-8) M) respectively. However, the time- and dose-dependent curves were biphasic with NPA and (+/-)-PPHT and the inhibition of cAMP production was abolished at higher agonist concentrations or after time incubations longer than 15 min. These inhibitions were receptor specific since they were reversed by spiperone and haloperidol, two specific--dopamine antagonist, and by butaclamol (mix D2/D1-dopamine antagonists) but not by alpha- and beta-adrenergic, D1- and D4-dopaminergic, and 5-HT2-serotonergic antagonists. The results reported here suggest that human placental D2 receptors interact with AC to inhibit its activity. Also, bromocriptine seems a better agonist for the characterization of dopaminergic effects on human placenta.