Ca2+ flux in human placental trophoblasts.
Intracellular Ca2+ is an important second messenger. In the placenta, regulation of intracellular Ca2+ concentration ([Ca2+]i) by extracellular factors has received relatively little attention. Cultured human placental trophoblasts were treated with a series of potential Ca(2+)-mobilizing ligands. After 3 days in culture, there was an increase in [Ca2+]i in response to angiotensin, endothelin, transforming growth factor-alpha, and ATP in approximately 8, 54, 17, and 100% of the cells, respectively. The response to ATP was dose dependent. At low ATP concentrations (1-10 microM), the response to repeat ATP application remained unchanged, whereas at 100 microM, response to repeat stimulation resulted in lower peak value. The order of potency for the ATP derivatives was ATP = UTP > benzoylbenzoic-ATP > ATP gamma S > ADP beta S > ADP > alpha,beta-MeATP > AMP. This suggests action via the P2u purinergic receptor. Removal of extracellular Ca2+ decreased the ATP-induced Ca2+ response by 45%; this indicates that a substantial portion of the increase in [Ca2+]i was due to influx from extracellular space. Finally, ATP rapidly induced inositol 1,4,5-trisphosphate formation in cultured trophoblasts. Therefore, ATP-induced changes in Ca2+ flux may be due in part to activation of phosphoinositide-specific phospholipase C. In summary, ATP is a potent calciotropic ligand in human placental trophoblasts, acting through the P2u receptor. The effect of ATP on [Ca2+]i may prove to be involved in the modulation of various trophoblast functions, including hormone secretion and active transport of nutrients.