Effects of extracellular nucleotides and nucleosides on prostate carcinomacells

I The purpose of this work was to characterize the receptors involved in th e action of nucleotides on the human prostate carcinoma cell lines LNCaP, P C-3 and DU145. 2 Northern blotting revealed the presence of P2Y(2), P2Y(6) and P2Y(11) mes sengers in the three cell lines. P2Y(1) mRNA was only observed in the DU145 cells. In both PC-3 and DU145 cells, ATP and UTP stimulated inositol phosp hate accumulation in an equipotent, equiactive and non-additive way, sugges ting the involvement of P2Y(2) receptors. ATP also increased cyclic AMP, bu t this effect is likely to result from degradation into adenosine and activ ation of A(2) receptor. A(2) receptor activation led to a synergistic enhan cement of prostate-specific antigen secretion induced by vasoactive intesti nal peptide. 3 RT-PCR experiments detected the expression of the P2X(4) and P2X(5) recep tors in the DU145 cells and the P2X(4). P2X(5) and P2X(7) receptors in the PC-3 cells. The calcium influx induced by BzATP confirmed the functional ex pression of P2X receptors. 4 ATP inhibited the growth of PC-3 and DU145 cells. This effect was mimicke d neither by UTP nor by adenosine, indicating that it does not result from phospholipase C or adenylyl cyclase activation. On the contrary, in PC-3 ce lls, BzATP reproduced the effect of ATP, which was associated to a moderate decrease of proliferation and an increase of apoptosis. In DU145 cells, AT P was more potent than BzATP and growth inhibition was mainly associated wi th necrosis. We suggest that P2X receptors might be involved in the inhibit ion by nucleotides of prostate carcinoma cell growth.