Pharmacological characterisation of pyrimidinoceptor responses in NG108-15 cells.
In the present study, the P2Y receptor(s) mediating the effects of the pyrimidines UTP and UDP on phospholipase C activation in the mouse neuroblastoma x rat glioma hybrid cell line NG108-15 was investigated. Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR) analysis detected transcripts for the P2Y(6) and P2Y(2) receptors, but not for P2Y(1) and P2Y(4.) UTP and UDP were equipotent agonists and their effects were partially additive. Suramin, reactive blue 2 and pyridoxal phosphate-6-azophenyl-2',4'disulfonic acid (PPADS) antagonised the phospholipase C response to both UTP and UDP. High micromolar concentrations of adenosine, 2-p-(2-carboxyethyl)phenethylamino-5'-N-ethylcarboxamidoadenosine (CGS-21680), 2',3'-O-isopropylideneadenosine (iPAdo) and adenosine 3':5'-cyclic monophosphate (3',5'-cAMP) were able to antagonise the effect of UTP on phospholipase C but not that of UDP. The additivity of the UTP and UDP responses, novel P2 receptor antagonist profile and the distinguishing action of adenosine may indicate the expression of a pyrimidine selective P2Y receptor in addition to the P2Y(6) type in these cells.
Institute of Chemical Physics, Tartu University, 2 Jakobi St., 51014, Tartu, Estonia. sak@chem.ut.ee
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Webb
D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology; D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D002460:Cell Line; D007295:Inositol Phosphates / Q000378:metabolism*; D051379:Mice; D051381:Rats; D018048:Receptors, Purinergic P2 / Q000187:drug effects* / Q000378:metabolism; D058472:Receptors, Purinergic P2Y1; D058473:Receptors, Purinergic P2Y2; D013498:Suramin / Q000494:pharmacology; D010738:Type C Phospholipases / Q000187:drug effects* / Q000378:metabolism; D014530:Uridine Diphosphate / Q000494:pharmacology*; D014544:Uridine Triphosphate / Q000494:pharmacology*
D000700:Analgesics; D000970:Antineoplastic Agents; D007295:Inositol Phosphates; C546383:P2ry1 protein, mouse; C546384:P2ry1 protein, rat; C546386:P2ry2 protein, mouse; C546387:P2ry2 protein, rat; D018048:Receptors, Purinergic P2; D058472:Receptors, Purinergic P2Y1; D058473:Receptors, Purinergic P2Y2; C104749:purinoceptor P2Y4; C099845:purinoceptor P2Y6; D014530:Uridine Diphosphate; D013498:Suramin; D010738:Type C Phospholipases; D000241:Adenosine; D014544:Uridine Triphosphate