title: Evaluation of reactive blue 2 derivatives as selective antagonists for P2Y receptors.
abstract: P2Y receptor pharmacology is hampered by a lack of subtype selective antagonists. However, a recent study evaluated series of compounds, structurally related to the dye reactive blue 2, for their antagonist selectivity at P2X vs. P2Y receptors. Acid blue 129, acid blue 80, acid blue 25 and acid violet 34 were found to be the most potent of the antagonists studied, at P2Y receptors [Naunyn Schmiedeberg's Arch. Pharmacol. 357 (1998) 111]. In this study, we have determined the ability of these four agents to selectively antagonize inositol phosphate turnover mediated by P2Y1 and P2Y2 receptors that are natively expressed in bovine aortic endothelial (BAE) cells. Acid blue 129, acid blue 80, and acid violet 34 shifted the dose-response curve of the P2Y1 agonist 2-methylthio adenosine trisphosphate (2MeSATP) to the right. Acid blue 129 and acid blue 80 were also very weak antagonists of the P2Y2 agonist uridine 5'-triphosphate (UTP). At 30 and 100 microM, acid violet 34 failed to have any significant effect on the dose-response to UTP. However, at 10 microM, acid violet 34 enhanced the UTP responses. Acid blue 80, acid blue 129 and acid violet 34 are P2Y vs. P2X selective, but show poor selectivity between P2Y1 and P2Y2 receptors and are therefore of limited use in the field of P2Y receptor pharmacology. Furthermore, contrary to previous reports, acid blue 25 is not a P2Y-selective antagonist.
authors.affiliation: Biomedical Sciences Division, School of Applied Sciences, University of Wolverhampton, Wulfruna Street, Wolverhampton WV1 1SB, UK. bia30@keele.ac.uk
authors.forename: Julia
authors.initials: J
authors.lastname: Brown
authors.forename: Colin A
authors.initials: CA
authors.lastname: Brown
mesh_terms: D000255:Adenosine Triphosphate / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000494:pharmacology; D000818:Animals; D000880:Anthraquinones / Q000494:pharmacology; D002417:Cattle; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D066298:In Vitro Techniques; D007295:Inositol Phosphates / Q000378:metabolism; D058919:Purinergic P2 Receptor Antagonists; D058472:Receptors, Purinergic P2Y1; D058473:Receptors, Purinergic P2Y2; D013873:Thionucleotides / Q000037:antagonists & inhibitors / Q000494:pharmacology; D014227:Triazines / Q000494:pharmacology*; D014544:Uridine Triphosphate / Q000037:antagonists & inhibitors / Q000494:pharmacology
chemical_list: D000880:Anthraquinones; D007295:Inositol Phosphates; D058919:Purinergic P2 Receptor Antagonists; D058472:Receptors, Purinergic P2Y1; D058473:Receptors, Purinergic P2Y2; D013873:Thionucleotides; D014227:Triazines; C012842:Cibacron Blue F 3GA; D000255:Adenosine Triphosphate; C433873:acid blue 80; D014544:Uridine Triphosphate; C008501:2-methylthio-ATP