PPADS INHIBITS P2Y(1) PURINOCEPTORS IN RAT-BRAIN CAPILLARY ENDOTHELIAL-CELLS AND IN RAT ILEAL MYOCYTES BY AN INDIRECT MECHANISM

P2Y(1) receptor-like responses were analyzed in rat ileal myocytes and in rat brain capillary endothelial cells. In endothelial cells, pyrid oxal phosphate-6-azophenyl-2',4'-disulfonic acid (PPADS) inhibits ADP induced intracellular Ca2+ transients with a half maximum effect at 3 mu M. PPADS shifts ADP dose response curves to larger concentrations. Yet PPADS is inactive when added at the same time as ADP. A preequilib ration of the cells with PPADS is necessary to observe its inhibitory action. Similarly in ileal myocytes, PPADS has no action on ADP respon ses when it is applied at the same time as ADP. Actions of PPADS requi re a preequilibration with the cells and are fully reversible, These r esults suggest that PPADS is not a competitive antagonist of P2Y(1) re ceptors and caution about its usefulness to distinguish subtypes of P2 Y(1) receptors. (C) 1998 Academic Press.