Pharmacological characterization of the human P2Y11 receptor.
1 The human P2Y11 receptor is coupled to both the phosphoinositide and the cyclic AMP pathways. A pharmacological characterization of the recombinant human P2Y11 receptor has been conducted following stable expression in two different cell lines: the 1321N1 astrocytoma cells for inositol trisphosphate measurements and the CHO-K1 cells for cyclic AMP assays. The rank order of potency of a series of nucleotides was almost identical for the two pathways: ATPgammaS approximately BzATP > dATP > ATP > ADPbetaS > 2MeSATP. 2 ADPbetaS, AMPalphaS and A3P5PS behaved as partial agonists of the human P2Y11 receptor. At high concentrations, these three nucleotides were able to partially inhibit the ATP response. 3 Suramin was a more potent antagonist than reactive blue 2, whereas pyridoxal-phosphate-6-azophenyl-2',4'-disulphonic acid was completely inactive. The P2Y11 receptor proved to be sensitive to suramin in a competitive way with an apparent Ki value of 0.82+/-0. 07 microM. 4 The ATP derivative AR-C67085 (2-propylthio-beta, gamma-dichloromethylene-D-ATP), a potent inhibitor of ADP-induced platelet aggregation, was the most potent agonist of the P2Y11 receptor, among the various nucleotides tested. 5 The pharmacological profile of the recombinant human P2Y11 receptor is closely similar to that of the cyclic AMP-coupled P2 receptor recently described in HL-60 cells, suggesting that it is the same receptor.
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Institute of Interdisciplinary Research, School of Medicine, Université Libre de Bruxelles, 808 Route de Lennik, 1070 Brussels, Belgium.
Robaye
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Boeynaems
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D000244:Adenosine Diphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D000249:Adenosine Monophosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D000242:Cyclic AMP / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006801:Humans; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D010724:Phosphoadenosine Phosphosulfate / Q000494:pharmacology; D058910:Purinergic P2 Receptor Agonists; D058919:Purinergic P2 Receptor Antagonists; D018048:Receptors, Purinergic P2 / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000819:agonists / Q000037:antagonists & inhibitors / Q000235:genetics; D013498:Suramin / Q000494:pharmacology; D013806:Theophylline / Q000031:analogs & derivatives / Q000494:pharmacology; D013873:Thionucleotides / Q000494:pharmacology; D013997:Time Factors; D014227:Triazines / Q000494:pharmacology; D014407:Tumor Cells, Cultured
C096709:FPL 67085; C109734:P2RY11 protein, human; D058910:Purinergic P2 Receptor Agonists; D058919:Purinergic P2 Receptor Antagonists; D018048:Receptors, Purinergic P2; D011993:Recombinant Fusion Proteins; D013873:Thionucleotides; D014227:Triazines; C030812:adenosine 5'-O-(2-thiodiphosphate); C045716:adenosine 2',5'-diphosphate; D000249:Adenosine Monophosphate; D010724:Phosphoadenosine Phosphosulfate; C012842:Cibacron Blue F 3GA; D013498:Suramin; D000244:Adenosine Diphosphate; C031433:8-(4-sulfophenyl)theophylline; D015544:Inositol 1,4,5-Trisphosphate; D000255:Adenosine Triphosphate; D013806:Theophylline; C010840:adenosine 3'-phosphate-5'-phosphate; D000242:Cyclic AMP