PC12 cells were used as a model system to examine drug effects on dopamine synthesis and release. It could be demonstrated that KCl treatment induced release of endogenous dopamine, simultaneously DOPA synthesis was increased. Despite of the increase in DOPA synthesis the intracellular concentration of tetrahydrobiopterin (the co-factor of tyrosine hydroxylase) remained stable, indicating that the catalytic recycling of the used tetrahydrobiopterin is much more rapid than the tetrahydrobiopterin consumption by tyrosine hydroxylation. Reserpine induced a decrease of intracellular dopamine but no dopamine reached the extracellular space, instead all dopamine was depleted into the cytoplasma and metabolized to DOPAC. Nitrendipine had no effect on intracellular dopamine storage, Bay K 8644 induced a small decrease of intracellular dopamine and a small increase in DOPA production. N-(6-aminohexyl)-5-chloro-1-naphthalene sulfonamide (W7) induced a reserpine-like depletion at concentrations above 1 X 10(-6) M. The KCl-induced dopamine release and the stimulation of DOPA production were blocked by 1 X 10(-7) M nitrendipine and enhanced by 1 X 10(-7) M Bay K 8466, whereas 1 X 10(-6) M W7 had no effect on both parameters. These findings were compared to data obtained in other tissues reported in the literature indicating that PC12 cells are a useful model for studying drug effects on catecholamine synthesis and release.