CA2+ FLUX IN HUMAN PLACENTAL TROPHOBLASTS

Intracellular Ca2+ is an important second messenger. In the placenta, regulation of intracellular Ca2+ concentration ([Ca2+](i)) by extracel lular factors has received relatively little attention. Cultured human placental trophoblasts were treated with a series of potential Ca2+-m obilizing ligands. After 3 days in culture, there was an increase in [ Ca2+](i) in response to angiotensin, endothelin, transforming growth f actor-alpha, and ATP in similar to 8, 54, 17, and 100% of the cells, r espectively. The response to ATP was dose dependent. At low ATP concen trations (1-10 mu M), the response to repeat ATP application remained unchanged, whereas at 100 mu M, response to repeat stimulation resulte d in lower peak value. The order of potency for the ATP derivatives wa s ATP = UTP > benzoylbenzoic-ATP > ATP gamma S > ADP beta S > ADP > al pha,beta-MeATP > AMP. This suggests action via the P-2u, purinergic re ceptor. Removal of extracellular Ca2+ decreased the ATP-induced Ca2+ r esponse by 45%; this indicates that a substantial portion of the incre ase 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 troph oblasts, 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 nutrien ts.