The C6-2B glioma cell P2Y(AC) receptor is pharmacologically and molecularly identical to the platelet P2Y(12) receptor

1 P2Y receptor activation in many cell types leads to phospholipase C activ ation and accumulation of inositol phosphates, while in blood platelets, C6 -2B glioma cells, and in B10 microvascular endothelial cells a P2Y receptor subtype, which couples to inhibition of adenylyl cyclase, historically ter med P2Y(AC), (P2T(AC) or P-2T in platelets) has been identified. Recently, this receptor has been cloned and designated P2Y(12) in keeping with curren t P2 receptor nomenclature. 2 Three selective P-2T receptor antagonists, with a range of affinities, in hibited ADP-induced aggregation of washed human or rat platelets, in a conc entration-dependent manner, with a rank order of antagonist potency (pIC(50 ), human: rat) of AR-C78511 (8.5:9.1)>AR-C69581 (6.2:6.0)>AR-C70300 (5.4:5. 1). However, these compounds had no effect on ADP-induced platelet shape ch ange. 3 All three antagonists had no significant effect on the ADP-induced inosit ol phosphate formation in 1321N1 astrocytoma cells stably expressing the P2 Y(1) receptor, when used at concentrations that inhibit platelet aggregatio n. 4 These antagonists also blocked ADP-induced inhibition of adenylyl cyclase in rat platelets and C6-2B cells with identical rank orders of potency and overlapping concentration-response curves. 5 RT-PCR and nucleotide sequence analyses revealed that the C6-2B cells exp ress the P2Y(12) mRNA. 6 These data demonstrate that the P2Y(AC) receptor in C6-2B cells is pharma cologically identical to the P2T(AC) receptor in rat platelets.