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 Ca²⁺- mobilizing ligands. After 3 days in culture, there was an increase in [Ca²⁺](i) in response to angiotensin, endothelin, transforming growth factor-α, and ATP in ~8, 54, 17, and 100% of the cells, respectively. The response to ATP was dose dependent. At low ATP concentration (1-10 μM), the response to repeat ATP application remained unchanged, whereas at 100 μM, response to repeat stimulation resulted in lower peak value. The order of potency for the ATP derivatives was ATP = UTP > benzoylbenzoic-ATP > ATPγS > ADPβS > ADP > α,β-MeATP > AMP. This suggests action via the P(2u) 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 P(2u) 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.