Activation of adenosine A1 receptors, A3 receptors, or histamine H3 receptors increases ALDH2 activity in PC12-H3 cells. Incubation of PC12-H3 cells with the selective ALDH2 activator Alda-1 (100 μM; 20 min) increases ALDH2 activity (measured by the rate of NADH production at 340 nm). A, incubation of PC12-H3 cells with the A1-receptor agonist 2′-MeCCPA (10 nM; 20 min) increases ALDH2 activity. Selective desensitization of ALDH2 with GTN (2 μM; 30 min) prevents the effects of Alda-1 and A1-receptor agonist. Pretreatment of PC12-H3 cells with the selective A1-receptor antagonist DPCPX (300 nM; 30 min) or the selective PKCε inhibitor εV1–2 (1 μM; 30 min) prevents the effects of A1-receptor activation. B, incubation of PC12-H3 cells with the A3-receptor agonist IB-MECA (50 nM; 20 min) increases ALDH2 activity. Selective desensitization of ALDH2 with GTN (2 μM; 30 min) prevents the effects of Alda-1 and IB-MECA. Pretreatment of PC12-H3 cells with the selective A3-receptor antagonist MRS1523 (100 nM; 30 min) or the selective PKCε inhibitor εV1–2 (1 μM; 30 min) prevents the effects of A3-receptor activation. C, incubation of PC12-H3 cells with the H3-receptor agonist methimepip (1 nM; 20 min) increases ALDH2 activity. Selective desensitization of ALDH2 with GTN (2 μM; 30 min) prevents the effects of Alda-1 and methimepip. Pretreatment of PC12-H3 cells with the selective H3-receptor antagonist JNJ5207852 (30 nM; 30 min) or the selective PKCε inhibitor εV1–2 (1 μM; 30 min) prevents the effects of H3-receptor activation. Bars are mean percentage increases from control (± S.E.M.; n = 4–16). Basal NADH production was 7.47 ± 0.13 μmol/min/mg protein. ***, P < 0.0001 from control. †††, P < 0.0001 from Alda-1. ♦♦♦, P < 0.0001 from A1R agonist. ‡‡‡, P < 0.001 from A3R agonist. ###, P < 0.0001 from methimepip by unpaired t test.