PPADS inhibits P2Y1 purinoceptors in rat brain capillary endothelial cells and in rat ileal myocytes by an indirect mechanism.
P2Y1 receptor-like responses were analyzed in rat ileal myocytes and in rat brain capillary endothelial cells. In endothelial cells, pyridoxal phosphate-6-azophenyl-2',4'disulfonic acid (PPADS) inhibits ADP induced intracellular Ca2+ transients with a half maximum effect at 3 microM. PPADS shifts ADP dose response curves to larger concentrations. Yet PPADS is inactive when added at the same time as ADP. A preequilibration of the cells with PPADS is necessary to observe its inhibitory action. Similarly in ileal myocytes, PPADS has no action on ADP responses when it is applied at the same time as ADP. Actions of PPADS require a preequilibration with the cells and are fully reversible. These results suggest that PPADS is not a competitive antagonist of P2Y1 receptors and caution about its usefulness to distinguish subtypes of P2Y1 receptors.
Vigne
P
P
Institut de Pharmacologie Moléculaire et Cellulaire, CNRS UPR 411, Valbonne, France.
Pacaud
P
P
Loirand
G
G
Breittmayer
J P
JP
Frelin
C
C
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000818:Animals; D001921:Brain / Q000098:blood supply; D002118:Calcium / Q000378:metabolism; D002999:Clone Cells; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D007082:Ileum / Q000187:drug effects / Q000378:metabolism; D066298:In Vitro Techniques; D007424:Intracellular Fluid / Q000378:metabolism; D007700:Kinetics; D009130:Muscle, Smooth / Q000187:drug effects / Q000378:metabolism; D058919:Purinergic P2 Receptor Antagonists; D011732:Pyridoxal Phosphate / Q000031:analogs & derivatives* / Q000494:pharmacology; D051381:Rats; D058472:Receptors, Purinergic P2Y1
C546384:P2ry1 protein, rat; D058919:Purinergic P2 Receptor Antagonists; D058472:Receptors, Purinergic P2Y1; C077792:pyridoxal phosphate-6-azophenyl-2',4'-disulfonic acid; D011732:Pyridoxal Phosphate; D000244:Adenosine Diphosphate; D002118:Calcium