AN ISLET-ACTIVATING PROTEIN-SENSITIVE G-PROTEIN IS INVOLVED IN DOPAMINE-INHIBITION OF BOTH ANGIOTENSIN-STIMULATED INOSITOL PHOSPHATE PRODUCTION AND HUMAN PLACENTAL-LACTOGEN RELEASE IN HUMAN TROPHOBLASTIC CELLS

In isolated human trophoblastic cells, dopamine (DA) significantly inhibited the angiotensin-II (All)-stimulated inositol phosphate (IP) accumulation by 44 ± 8% (EC60, 0.5 ± 0.2 μM) and human placental lactogen (hPL) release by 85 ± 5% (EC60, 1.0 ± 0.8 μM). These effects were blocked by sulpiride, a specific D2 antagonist. On the contrary, scherring 23390 (a specific D1 antagonist) and propranolol (a specific β-adrenergic antagonist) were ineffective, suggesting that these DA effects are mediated through a DA receptor of the D2 subtype. The mechanism by which DA inhibited All-stimulated inositol phosphate production implicates a GTP-binding protein sensitive to the islet-activating-protein (IAP), since DA’s effects on IP accumulation and hPL Release were blocked by this toxin. To further characterize this GTP-binding protein, particulate fractions of placental cells were incubated with [α-32P]NAD and IAP. Solubilized extracts were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Two proteins of 40 and 41 kDa mol wt were specifically ADP ribosylated. They were probably involved in the DA inhibitory processes, since IAP treatment, known to suppress the effects of DA, also reduced the labeling of these two molecules by around 40%. The effects of All and DA on hPL release appear to be insensitive to the external calcium concentration, since the results were not significantly different in normal (1.8 mM Ca2+) and low Ca2+ (10−5M Ca2+) concentrations. On the other hand, increasing the intracellular concentration of cAMP by adding forskolin did not modify the effect of DA on either IP accumulation or hPL release, suggesting that cAMP is not implicated in hPL release from freshly isolated human trophoblastic cells. © 1990 by The Endocrine Society.