phosphatidylethanol and Ovarian-Neoplasms

In human ovarian EFO-21 and EFO-27 carcinoma cells, extracellular ATP induced a concentration-dependent rise in intracellular calcium concentration ([Ca(2+)](i)), suggesting the expression of a purinoreceptor. ATP and UTP were equipotent in generating [Ca(2+)](i) signals, followed by ATP-gamma-S and ADP, whereas beta, gamma-ATP, 2 methyl 1 thio-ATP, 3'-o-(4-benzoyl) benzoyl-ATP, AMP, and adenosine were ineffective. This pharmacological profile suggested the presence of the P2Y(2) subtype in both cell types, and this was confirmed by reverse transcription-polymerase chain reaction (RT-PCR) analysis using P2Y(2) primers. ATP-induced [Ca(2+)](i) signals were composed of two phases: an early and extracellular calcium-independent phase, followed by a sustained plateau phase that was dependent on capacitative calcium influx. In addition to the rise in the [Ca(2+)](i), a time- and concentration-dependent increase in phosphatidylethanol accumulation was observed in ATP-stimulated cells, indicating an increase in phospholipase D activity. RT-PCR analysis identified the expression of a transcript for the phospholipase D-1 subtype of this enzyme. Activation of these receptors by a slowly degradable analogue, ATP-gamma-S, attenuated basal and fetal calf serum-induced cell proliferation in a time- and concentration-dependent manner. These results indicate that ATP may act as an extracellular messenger in controlling the ovarian epithelial cell cycle through P2Y(2) receptors.

Topics: Adenosine Triphosphate; Calcium; Calcium Channel Blockers; Cell Division; Dihydropyridines; Enzyme Activation; Enzyme Inhibitors; Female; Glycerophospholipids; Humans; Nifedipine; Ovarian Neoplasms; Phospholipase D; Potassium; Receptors, Purinergic P2; Receptors, Purinergic P2Y2; Thapsigargin; Tumor Cells, Cultured; Uridine Triphosphate