K+-induced depolarization of NGF-differentiated PC12 cells elicits the release of ATP and dopamine, which is attenuated in CD39-overexpressing PC12 cells. The addition of solCD39 mimics the effects of ENTPDase1/CD39 overexpression. In contrast, CD39-silencing enhances the depolarization-induced release of ATP and dopamine. For K+-induced depolarization cells were incubated with 100 mM K+ for 10 min; ATP and dopamine were assayed at the end of the 10-min incubation period. Bars are means (±S.E.M.; n = 3–34) of percentage increases in ATP (C and D) and dopamine (A and B) release over control from basal levels (ATP, 18.0 ± 2.0 nM; dopamine, 7.7 ± 1.8 nM). *, P < 0.05; **, P < 0.01; ***, P < 0.001 from wild-type control by one-way ANOVA followed by Dunnett's multiple comparison test.