TY - JOUR T1 - ATP Derivatives Are Antagonists of the P2Y<sub>1</sub> Receptor: Similarities to the Platelet ADP Receptor JF - Molecular Pharmacology JO - Mol Pharmacol SP - 727 LP - 733 DO - 10.1124/mol.53.4.727 VL - 53 IS - 4 AU - Béatrice Hechler AU - Paul Vigne AU - Catherine Léon AU - Jean-Philippe Breittmayer AU - Christian Gachet AU - Christian Frelin Y1 - 1998/04/01 UR - http://molpharm.aspetjournals.org/content/53/4/727.abstract N2 - Pharmacological properties of the human P2Y1 receptor transfected in Jurkat cells and of the endogenous receptor in rat brain capillary endothelial cells were analyzed under conditions in which the purity of adenine triphosphate nucleotides was controlled by creatine phosphate/creatine phosphokinase (CP/CPK). ATP, a partial agonist of the receptor, was inactive in the presence of CP/CPK. Results further indicated that ATP was a competitive antagonist of ADP actions.K i values were 23.0 ± 1.5 μm in endothelial cells and 14.3 ± 0.3 μm in Jurkat cells. Solutions prepared from commercially available 2-methylthio-ATP (2-MeSATP) or 2-chloro-ATP (2-ClATP) contained ≈10% of ADP derivatives. ADP derivatives were removed from the solution by treatment with CP/CPK. Purified 2-MeSATP and 2-ClATP antagonized platelet aggregation induced by ADP. They did not activate P2Y1 receptors but prevented ADP actions in a competitive manner. K i values for 2-MeSATP were 36.5 μm in endothelial cells and 5.7 ± 0.4 μm in Jurkat cells, andK i values for 2-ClATP were 27.5 μm in endothelial cells and 2.3 ± 0.3 μm in Jurkat cells. EDTA potentiated actions of ADP and ATP on endothelial cells by 2.4- and 3.6-fold, respectively. In conclusion, the rat and human P2Y1 receptors are ADP-specific receptors that recognize ADP and 2-methylthio-ADP, whereas ATP, 2-MeSATP, and 2-ClATP are competitive antagonists. The results further point to the close pharmacological similarity of the P2Y1 receptor and the platelet ADP receptor. ER -