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 structural 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 mixture was analysed. It was found that transformation of this ligand to ADP was responsible for initiation of synthesis of inositol phosphates, observed 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 antagonist at P2Y(1) receptors and was characterized by the apparent inhibitory constant 5 microM.
Sak
K
K
Institute of Chemical Physics, Tartu University, 2 Jakobi St. 51014, Tartu, Estonia. sak@chem.ut.ee
Järv
J
J
D000244:Adenosine Diphosphate / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000378:metabolism / Q000494:pharmacology*; D002460:Cell Line; D003402:Creatine Kinase / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006207:Half-Life; D006801:Humans; D007295:Inositol Phosphates / Q000378:metabolism; D010725:Phosphocreatine / Q000378:metabolism; D010766:Phosphorylation; D058910:Purinergic P2 Receptor Agonists; D058919:Purinergic P2 Receptor Antagonists; D018048:Receptors, Purinergic P2 / Q000378:metabolism; D058472:Receptors, Purinergic P2Y1; D013873:Thionucleotides / Q000037:antagonists & inhibitors / Q000494:pharmacology
D007295:Inositol Phosphates; C546382:P2RY1 protein, human; D058910:Purinergic P2 Receptor Agonists; D058919:Purinergic P2 Receptor Antagonists; D018048:Receptors, Purinergic P2; D058472:Receptors, Purinergic P2Y1; D013873:Thionucleotides; D010725:Phosphocreatine; C002480:methylthio-ADP; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D003402:Creatine Kinase