A. Schultze-mosgau et al., Characterization of calcium-mobilizing, purinergic P2Y(2) receptors in human ovarian cancer cells, MOL HUM REP, 6(5), 2000, pp. 435-442
In human ovarian EFO-21 and EFO-27 carcinoma cells, extracellular ATP induc
ed a concentration-dependent rise in intracellular calcium concentration ([
Ca2+](i)). suggesting the expression of a purinoreceptor. ATP and UTP were
equipotent in generating [Ca2+](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 suggest
ed the presence of the P2Y(2) subtype in both cell types, and this was conf
irmed by reverse transcription-polymerase chain reaction (RT-PCR) analysis
using P2Y(2) primers. ATP-induced [Ca2+](i) signals were composed of two ph
ases: an early and extracellular calcium-independent phase, followed by a s
ustained plateau phase that was dependent on capacitative calcium influx. I
n addition to the rise in the [Ca2+](i), a time- and concentration-dependen
t increase in phosphatidylethanol accumulation was observed in ATP-stimulat
ed cells, indicating an increase in phospholipase D activity. RT-PCR analys
is identified the expression of a transcript for the phospholipase D-1 subt
ype of this enzyme. Activation of these receptors by a slowly degradable an
alogue, ATP-gamma-S, attenuated basal and fetal calf serum-induced cell pro
liferation in a time- and concentration-dependent manner. These results ind
icate that ATP may act as an extracellular messenger in controlling the ova
rian epithelial cell cycle through P2Y(2) receptors.