Dual effect of nucleotides on P2Y receptors.
The interaction of ADP, 2MeSADP, and ADPbetaS with the adenine nucleotide receptor P2Y1 in the hP2Y1-1321N1 cell line and of UDP with a receptor or receptors recognizing pyrimidine nucleotides in NG108-15 cells was studied over a wide range ofligand concentrations. Bell-shaped dose-response curves for stimulation of phosphoinositide hydrolysis were obtained in these cells. This dual behavior of the agonists studied was characterized by two dissociation constants, K(agon) and K(antag), which quantify the agonistic and antagonistic activity of these ligands and can be compared with the conventional EC50 and IC50 values, respectively. The data revealed a common pattern of agonistic and antagonistic behavior of nucleoside diphosphates and their derivatives at these two types of P2Y receptors, pointing to some similar properties of their nucleotide binding sites.
Sak
K
K
Institute of Chemical Physics, Tartu University, Estonia.
Barnard
E A
EA
Järv
J
J
D000244:Adenosine Diphosphate / Q000031:analogs & derivatives* / Q000378:metabolism; D001665:Binding Sites; D002118:Calcium / Q000494:pharmacology; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D006801:Humans; D006868:Hydrolysis; D020128:Inhibitory Concentration 50; D007477:Ions; D007700:Kinetics; D008024:Ligands; D008274:Magnesium / Q000494:pharmacology; D009711:Nucleotides / Q000378:metabolism*; D010716:Phosphatidylinositols / Q000378:metabolism; D058910:Purinergic P2 Receptor Agonists; D058919:Purinergic P2 Receptor Antagonists; D018048:Receptors, Purinergic P2 / Q000378:metabolism*; D058472:Receptors, Purinergic P2Y1; D013873:Thionucleotides / Q000378:metabolism; D014407:Tumor Cells, Cultured; D014530:Uridine Diphosphate / Q000378:metabolism
D007477:Ions; D008024:Ligands; D009711:Nucleotides; C546382:P2RY1 protein, human; D010716:Phosphatidylinositols; D058910:Purinergic P2 Receptor Agonists; D058919:Purinergic P2 Receptor Antagonists; D018048:Receptors, Purinergic P2; D058472:Receptors, Purinergic P2Y1; D013873:Thionucleotides; C002480:methylthio-ADP; C030812:adenosine 5'-O-(2-thiodiphosphate); D014530:Uridine Diphosphate; D000244:Adenosine Diphosphate; D008274:Magnesium; D002118:Calcium