Adenosine triphosphate is full antagonist at human P2Y(1) purinoceptors

Both agonistic and antagonistic effects have been reported for ATP at P2Y(1 ) purinoceptors at micromolar ligand concentrations. These conflicting data hamper specification of the true pharmacological profile as well as struct ural requirements for antagonistic ligands of this receptor. in this report the type of ATP activity at human P2Y(1) receptors in hP2Y(1)-1321N1 cells was revisited. In parallel, kinetics of degradation of ATP in the assay mi xture was analysed. It was found that transformation of this ligand to ADP was responsible for initiation of synthesis of inositol phosphates. observe d in the presence of ATP in hP2Y(1)-1321N1 cells. This agonistic effect was abolished in the presence of the triphosphate regeneration system (CP/CPK) . On the other hand, if the agonistic effect caused by degradation product of ATP was taken into consideration, this ligand behaved as a full antagoni st at P2Y(1) receptors and was characterized by the apparent inhibitory con stant 5 mu M. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.