Pharmacological characterization of the human P2Y4 receptor.
The P2Y4 receptor is a new member of the P2Y family which functionally behaves as a pyrimidinergic receptor. The pharmacological properties of the human P2Y4 receptor have been characterized following its stable expression in 1321N1 astrocytoma cells. UTP induced a biphasic accumulation of inositol trisphosphates, with an early peak at 30 s followed by a smaller but more sustained accumulation. ATP was a pure antagonist at early times and later behaved as a partial agonist. At 20 min, the rank order of potency of various nucleotides was the following: UTP > UDP = deoxy UTP > 5-bromo-UTP > ITP > ATP. Diadenosine polyphosphates also stimulated the production of inositol trisphosphates (after 20 min), more potently than ATP, but their maximal effect represented only 20-25% of that of UTP. Pyridoxal-phosphate-6-azophenyl-2',4'-disulphonic acid inhibited strongly the UTP response, whereas suramin was inactive and reactive blue 2 had an intermediate effect. Pertussis toxin inhibited the response to UTP at early times (62 +/- 5% inhibition at 30 s), but its effect was no longer observed at 5 or 20 min. It is speculated that the P2Y4 receptor can exist in two distinct activation states differing in terms of time-course, specificity for uridine nucleotides and G-protein coupling.
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Institute of Interdisciplinary Research, School of Medicine, Erasme Hospital, Université Libre de Bruxelles, Belgium.
Motte
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Boeynaems
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Pirotton
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D000255:Adenosine Triphosphate / Q000378:metabolism; D001254:Astrocytoma / Q000378:metabolism; D001932:Brain Neoplasms / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000378:metabolism; D006801:Humans; D009711:Nucleotides / Q000378:metabolism; D037342:Pertussis Toxin; D058910:Purinergic P2 Receptor Agonists; D058919:Purinergic P2 Receptor Antagonists; D011869:Radioligand Assay; D018048:Receptors, Purinergic P2 / Q000187:drug effects*; D014407:Tumor Cells, Cultured; D014500:Uracil Nucleotides / Q000378:metabolism; D014544:Uridine Triphosphate / Q000378:metabolism; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D009711:Nucleotides; D058910:Purinergic P2 Receptor Agonists; D058919:Purinergic P2 Receptor Antagonists; D018048:Receptors, Purinergic P2; D014500:Uracil Nucleotides; D010566:Virulence Factors, Bordetella; D000255:Adenosine Triphosphate; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins; D014544:Uridine Triphosphate