Pharmacological characterization of the human P2Y(11) receptor

1 The human P2Y(11) receptor is coupled to both the phosphoinositide and th e cyclic AMP pathways. A pharmacological characterization of the recombinan t human P2Y(11) receptor has been conducted following stable expression in two different cell lines: the 1321N1 astrocytoma cells for inositol trispho sphate measurements and the CHO-K1 cells for cyclic AMP assays. The rank or der of potency of a series of nucleotides was almost identical for the two pathways: ATP gamma S approximate to BzATP > dATP > ATP > ADP beta S > 2MeS ATP. 2 ADP beta S, AMP alpha S and A3P5PS behaved as partial agonists of the hum an P2Y(11) receptor. At high concentrations, these three nucleotides were a ble to partially inhibit the ATP response. 3 Suramin was a more potent antagonist than reactive blue 2, whereas pyrido xal-phosphate-6-azophenyl-2',4'-disulphonic acid was completely inactive. T he P2Y(11) receptor proved to be sensitive to suramin in a competitive way with an apparent K-i value of 0.82 +/- 0.07 mu M. 4 The ATP derivative AR-C67085 (2-propylthio-beta, gamma-dichloromethylene- D-ATP), a potent inhibitor of ADP-induced platelet aggregation, was the mos t potent agonist of the P2Y(11) receptor, among the various nucleotides tes ted. 5 The pharmacological profile of the recombinant human P2Y(11) receptor is closely similar to that of the cyclic AMP-coupled Pt receptor recently desc ribed in HL-60 cells, suggesting that it is the same receptor.