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

P2Y receptor activation in many cell types leads to phospholipase C activation 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 termed 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 current P2 receptor nomenclature. Three selective P 2T receptor antagonists, with a range of affinities, inhibited ADP‐induced aggregation of washed human or rat platelets, in a concentration‐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 change. All three antagonists had no significant effect on the ADP‐induced inositol phosphate formation in 1321N1 astrocytoma cells stably expressing the P2Y 1 receptor, when used at concentrations that inhibit platelet aggregation. 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. RT – PCR and nucleotide sequence analyses revealed that the C6‐2B cells express the P2Y 12 mRNA. These data demonstrate that the P2Y AC receptor in C6‐2B cells is pharmacologically identical to the P2T AC receptor in rat platelets.British Journal of Pharmacology (2001) 133 , 521–528; doi: 10.1038/sj.bjp.0704114