Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adenosine Diphosphate / analogs & derivatives
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Adenosine Diphosphate / pharmacology
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Adenosine Monophosphate / analogs & derivatives
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Adenosine Monophosphate / pharmacology
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Adenosine Triphosphate / analogs & derivatives
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Adenosine Triphosphate / pharmacology
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Animals
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CHO Cells
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Cricetinae
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Cyclic AMP / metabolism
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Dose-Response Relationship, Drug
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Humans
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Inositol 1,4,5-Trisphosphate / metabolism
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Phosphoadenosine Phosphosulfate / pharmacology
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Purinergic P2 Receptor Agonists*
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Purinergic P2 Receptor Antagonists*
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Receptors, Purinergic P2 / genetics
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Recombinant Fusion Proteins / agonists
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Recombinant Fusion Proteins / antagonists & inhibitors
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Recombinant Fusion Proteins / genetics
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Suramin / pharmacology
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Theophylline / analogs & derivatives
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Theophylline / pharmacology
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Thionucleotides / pharmacology
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Time Factors
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Triazines / pharmacology
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Tumor Cells, Cultured
Substances
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FPL 67085
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P2RY11 protein, human
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Purinergic P2 Receptor Agonists
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Purinergic P2 Receptor Antagonists
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Receptors, Purinergic P2
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Recombinant Fusion Proteins
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Thionucleotides
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Triazines
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adenosine 5'-O-(2-thiodiphosphate)
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adenosine 2',5'-diphosphate
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Adenosine Monophosphate
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Phosphoadenosine Phosphosulfate
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Cibacron Blue F 3GA
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Suramin
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Adenosine Diphosphate
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8-(4-sulfophenyl)theophylline
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Inositol 1,4,5-Trisphosphate
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Adenosine Triphosphate
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Theophylline
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adenosine 3'-phosphate-5'-phosphate
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Cyclic AMP