Inhibition of angiotensin II-stimulated inositol phosphate production by D2-dopamine receptor is calcium-dependent in human trophoblastic cells.
We previously reported that dopamine (DA) acted via D2-dopamine receptors in human trophoblastic cells to inhibit All-stimulated inositol phosphate (InsP) accumulation. However, the mechanism by which DA inhibited All-stimulated InsP accumulation is still unknown except that this inhibitory effect was sensitive to Pertussis toxin (PTX). In this study, we characterize this DA-mediated inhibition of All-stimulated InsP production in human placenta. Freshly isolated human term placental cells were prelabeled with myo-[2-3H]inositol and incubated with various stimuli in the presence of 10 mM LiCl. All (10(-6) M) stimulated 1.5 times the human trophoblastic cell InsP production whereas DA (10(-4) M) inhibited this All-stimulated InsP production by 54 +/- 7%. This inhibitory effect was mimicked by bromocriptine (53 +/- 3% of inhibition), a D2-dopamine agonist. We recently reported that bromocriptine inhibited human placental adenosine 3',5'-cyclic monophosphate (cAMP) production. Increasing the intracellular concentration of cAMP levels by adding forskolin did not modify the effect of DA and bromocriptine on InsP accumulation. On the other hand, the effect of DA and bromocriptine on All-stimulated InsP production were greatly affected by treatments that modify the cytosolic free Ca2+ concentration. Specifically, the D2-dopaminergic mediated inhibition was prevented by treatment of cells with the Ca2+ ionophore ionomycin (10(-5) M) and was mimicked either by removal of Ca2+ from incubation medium (53 +/- 6%) or by blockage of voltage-gated Ca2+ channels with nifedipine (51 +/- 7%). Our data indicate that the inhibitory effect of D2-dopamine agonists on All-stimulated InsP production is an indirect event probably due to the DA-inhibition of calcium influx.
Vaillancourt
C
C
Department of Obstetrics and Gynecology, University of Montreal, Hospital Ste-Justine, Québec, Canada.
Petit
A
A
Bélisle
S
S
D000804:Angiotensin II / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D001971:Bromocriptine / Q000494:pharmacology; D002118:Calcium / Q000502:physiology; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000502:physiology; D004298:Dopamine / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D007295:Inositol Phosphates / Q000378:metabolism*; D009543:Nifedipine / Q000494:pharmacology; D017448:Receptors, Dopamine D2 / Q000502:physiology*; D014327:Trophoblasts / Q000378:metabolism*
D007295:Inositol Phosphates; D017448:Receptors, Dopamine D2; D000804:Angiotensin II; D005576:Colforsin; D001971:Bromocriptine; D000242:Cyclic AMP; D009543:Nifedipine; D002118:Calcium; D004298:Dopamine