Extracellular nucleotides and nucleosides induce proliferation and increase nucleoside transport in human glioma cell lines.
Extracellular purines (adenosine triphosphate (ATP), adenosine 5'-diphosphate (ADP) and adenosine) and pyrimidines (uridine 5'-triphosphate (UTP) and UDP) are important signaling molecules that mediate diverse biological effects via P1 and P2 purinergic receptors. The human glioma cell lines U87 MG, U251 MG and U138 MG were treated with purines and pyrimidines for 24 or 48 h and proliferation was measured by [3H]-thymidine incorporation, flow cytometry and cell counting. The studies showed that extracellular nucleotides and nucleosides induce proliferation of the studied glioma cells. Incorporation of [3H]-thymidine followed the order of ATP approximately equal to guanosine approximately equal to inosine approximately equal to adenosine > UTP > ADP while ATPgammaS and 2MeSATP had no effect. The effect of ATP was partially inhibited by suramin and by reactive blue 2 (RB2). Co-treatment with the following antagonists of P1 purinoreceptors DPCPX, CPT or 8PT did not block the effect of adenosine while a specific antagonist of the A3 receptor, MRS1220, totally blocked the effect of adenosine. ATP and adenosine also increased the overall uptake of [3H]-thymidine into the cell, producing a positive effect on the [3H]-thymidine incorporation measurements. These data indicate that the uptake of thymidine and proliferation of gliomas can be induced by purines and pyrimidines via both P1 and P2 purinoceptors.
Morrone
Fernanda B
FB
Departamento de Bioquimica, ICBS Faculdade de Farmácia, PUCRS, Porto Alegre, RS, Brazil.
Jacques-Silva
Maria C
MC
Horn
Ana P
AP
Bernardi
Andressa
A
Schwartsmann
Gilberto
G
Rodnight
Richard
R
Lenz
Guido
G
D000241:Adenosine / Q000378:metabolism; D000244:Adenosine Diphosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D001932:Brain Neoplasms / Q000378:metabolism*; D002455:Cell Division / Q000502:physiology; D004247:DNA / Q000096:biosynthesis*; D005110:Extracellular Space / Q000378:metabolism; D005910:Glioma / Q000378:metabolism*; D006801:Humans; D009705:Nucleosides / Q000378:metabolism; D009711:Nucleotides / Q000378:metabolism; D058906:Purinergic P1 Receptor Agonists; D058910:Purinergic P2 Receptor Agonists; D011687:Purines / Q000378:metabolism*; D011743:Pyrimidines / Q000378:metabolism; D018047:Receptors, Purinergic P1 / Q000378:metabolism; D018048:Receptors, Purinergic P2 / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D013936:Thymidine / Q000378:metabolism; D014407:Tumor Cells, Cultured; D014530:Uridine Diphosphate / Q000378:metabolism*; D014544:Uridine Triphosphate / Q000378:metabolism*
D009705:Nucleosides; D009711:Nucleotides; D058906:Purinergic P1 Receptor Agonists; D058910:Purinergic P2 Receptor Agonists; D011687:Purines; D011743:Pyrimidines; D018047:Receptors, Purinergic P1; D018048:Receptors, Purinergic P2; D014530:Uridine Diphosphate; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D004247:DNA; D000241:Adenosine; D014544:Uridine Triphosphate; D013936:Thymidine