title: Functional interaction between purinergic receptors: effect of ligands for A2A and P2Y12 receptors on P2Y1 receptor function.
abstract: A(2A) adenosine receptor (A(2A)R), P2Y(1) receptor (P2Y(1)R) and P2Y(12) receptor (P2Y(12)R) are predominantly expressed on human platelets. The individual role of each of these receptors in platelet aggregation has been actively reported. Previously, hetero-oligomerization between these three receptors has been shown to occur. Here, we show that Ca(2+) signaling evoked by the P2Y(1)R agonist, 2-methylthioladenosine 5' diphosphate (2MeSADP) was significantly inhibited by the A(2A)R antagonist (ZM241385 (4-(2-[7-amino-2-(2-furyl)[1,2,4]-triazolo[2,3-α][1,3,5]triazin-5-yl amino]ethyl) phenol) and SCH442416) and the P2Y(12)R antagonist (ARC69931MX) (N6-(2-methyl-thioethyl)-2-(3,3,3-trifluoropropylthio)-β,γ-dichloromethylene-ATP)) using HEK293T cells expressing the three receptors. It was confirmed that inhibition of P2Y(1)R signaling by A(2A)R and P2Y(12)R antagonists was indeed mediated through A(2A)R and P2Y(12)R using 1321N1 human astrocytoma cells which do not express P2Y receptors. We expect that intermolecular signal transduction and specific conformational changes occur among components of hetero-oligomers formed by these three receptors.
authors.affiliation: Department of Cellular Signaling, Graduate School of Pharmaceutical Sciences, Tohoku University, Aramaki, Aoba-ku, Sendai, Japan. tokiko-s@aoni.waseda.jp
authors.forename: Tokiko
authors.initials: T
authors.lastname: Suzuki
authors.forename: Yutaro
authors.initials: Y
authors.lastname: Obara
authors.forename: Takahiro
authors.initials: T
authors.lastname: Moriya
authors.forename: Hiroyasu
authors.initials: H
authors.lastname: Nakata
authors.forename: Norimichi
authors.initials: N
authors.lastname: Nakahata
mesh_terms: D058917:Adenosine A2 Receptor Antagonists / Q000494:pharmacology; D020013:Calcium Signaling / Q000187:drug effects; D045744:Cell Line, Tumor; D005786:Gene Expression Regulation / Q000187:drug effects; D057809:HEK293 Cells; D006801:Humans; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism; D008024:Ligands; D011485:Protein Binding; D058912:Purinergic P2Y Receptor Agonists / Q000494:pharmacology; D058921:Purinergic P2Y Receptor Antagonists / Q000494:pharmacology; D043705:Receptor, Adenosine A2A / Q000378:metabolism*; D058472:Receptors, Purinergic P2Y1 / Q000378:metabolism*; D058925:Receptors, Purinergic P2Y12 / Q000378:metabolism*; D014227:Triazines / Q000494:pharmacology; D014230:Triazoles / Q000494:pharmacology
chemical_list: D058917:Adenosine A2 Receptor Antagonists; D008024:Ligands; D058912:Purinergic P2Y Receptor Agonists; D058921:Purinergic P2Y Receptor Antagonists; D043705:Receptor, Adenosine A2A; D058472:Receptors, Purinergic P2Y1; D058925:Receptors, Purinergic P2Y12; D014227:Triazines; D014230:Triazoles; C097270:ZM 241385