Pharmacological characterization of the human P2Y11 receptor

Br J Pharmacol. 1999 Nov;128(6):1199-206. doi: 10.1038/sj.bjp.0702909.

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

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Diphosphate / analogs & derivatives
  • Adenosine Diphosphate / pharmacology
  • Adenosine Monophosphate / analogs & derivatives
  • Adenosine Monophosphate / pharmacology
  • Adenosine Triphosphate / analogs & derivatives
  • Adenosine Triphosphate / pharmacology
  • Animals
  • CHO Cells
  • Cricetinae
  • Cyclic AMP / metabolism
  • Dose-Response Relationship, Drug
  • Humans
  • Inositol 1,4,5-Trisphosphate / metabolism
  • Phosphoadenosine Phosphosulfate / pharmacology
  • Purinergic P2 Receptor Agonists*
  • Purinergic P2 Receptor Antagonists*
  • Receptors, Purinergic P2 / genetics
  • Recombinant Fusion Proteins / agonists
  • Recombinant Fusion Proteins / antagonists & inhibitors
  • Recombinant Fusion Proteins / genetics
  • Suramin / pharmacology
  • Theophylline / analogs & derivatives
  • Theophylline / pharmacology
  • Thionucleotides / pharmacology
  • Time Factors
  • Triazines / pharmacology
  • Tumor Cells, Cultured

Substances

  • FPL 67085
  • P2RY11 protein, human
  • Purinergic P2 Receptor Agonists
  • Purinergic P2 Receptor Antagonists
  • Receptors, Purinergic P2
  • Recombinant Fusion Proteins
  • Thionucleotides
  • Triazines
  • adenosine 5'-O-(2-thiodiphosphate)
  • adenosine 2',5'-diphosphate
  • Adenosine Monophosphate
  • Phosphoadenosine Phosphosulfate
  • Cibacron Blue F 3GA
  • Suramin
  • Adenosine Diphosphate
  • 8-(4-sulfophenyl)theophylline
  • Inositol 1,4,5-Trisphosphate
  • Adenosine Triphosphate
  • Theophylline
  • adenosine 3'-phosphate-5'-phosphate
  • Cyclic AMP