Ticagrelor-mediated attenuation of agonist-dependent and agonist-independent P2Y₁₂R activity in 1321N1 cells. Inhibition of forskolin (1 µM; 10 minutes)–induced cAMP production by ADP (0.1 nM-100 µM; 10 minutes) in P2Y₁₂R-transfected 1321N1 cells after preincubation with ticagrelor (3-30 nM; 15 minutes) (A) or AR-C 66096 (AR-C; 3-30 nM; 15 minutes) (B); n = 5. (C) Schild-plot analysis of data from panels A and B. (D) Forskolin (0.1 nM-1 µM; 10 minutes)–induced increases in cAMP levels in pcNEO-transfected and P2Y₁₂R-transfected 1321N1 cells. (E) Forskolin (1 µM; 10 minutes)–induced cAMP production in pcNEO-transfected and P2Y₁₂-transfected cells incubated with vehicle (0.1% DMSO), ticagrelor (10 µM), AR-C 66096 (10 µM), or R-138727 (10 µM) for 30 minutes. (F) Forskolin (1 µM; 10 minutes)–induced cAMP after preincuabtion with vehicle (0.1% DMSO) or ticagrelor (0.01 µM-10 μM; 30 minutes) in P2Y₁₂R-transfected cells; n = 5. All graphs and bar charts display mean ± SEM. All cells were incubated with 0.2 U/mL apyrase (37°C; 60 minutes) prior to drug additions. *P < .05 vs pcNEO controls.