adp-beta-s and adenosine-3--phosphate-5--phosphate

Since the beginning of purinoceptor research turkey erythrocytes have been widely used as the model systems for studying the pharmacology of P2Y1 nucleotide receptors. In this report the statistical analysis of the activity parameters of several purinoceptor agonists and antagonists in the turkey erythrocytes and P2Y1 receptor transfected cells is presented. As a results of this analysis several differences in the ligand activity orders measured in these biological systems were found. These data indicate that the receptors expressed in turkey erythrocytes and P2Y1 transfected cells are probably not the same. Whether it has to do with co-expression of several purinoceptor subtypes in turkey erythrocytes or novel P2Y receptors needs the further investigation.

Topics: Adenosine Diphosphate; Adenosine Triphosphate; Animals; Erythrocytes; Ligands; Purinergic P2 Receptor Agonists; Purinergic P2 Receptor Antagonists; Receptors, Purinergic P2; Receptors, Purinergic P2Y1; Thionucleotides; Transfection; Turkeys

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.

Topics: Adenosine Diphosphate; Adenosine Monophosphate; Adenosine Triphosphate; Animals; CHO Cells; Cricetinae; Cyclic AMP; Dose-Response Relationship, Drug; Humans; Inositol 1,4,5-Trisphosphate; Phosphoadenosine Phosphosulfate; Purinergic P2 Receptor Agonists; Purinergic P2 Receptor Antagonists; Receptors, Purinergic P2; Recombinant Fusion Proteins; Suramin; Theophylline; Thionucleotides; Time Factors; Triazines; Tumor Cells, Cultured