Activation of tyrosine hydroxylase by micromolar concentrations of calcium in digitonin-permeabilized adrenal medullary cells.

In digitonin-permeabilized bovine adrenal medullary cells, Ca2+ (0.1-1.0 microM) caused an activation of tyrosine hydroxylase which was dependent on the presence of ATP. This Ca2+-induced activation of the enzyme was observed even in the presence of optimal concentration of either cyclic AMP or 12-O-tetradecanoylphorbol-13-acetate (TPA) which by itself increased the enzyme activity. Calmodulin inhibitors, trifluoperazine (TFP) and N-(6-aminohexyl)-5-chloro-1-naphtalenesulfonamide (W-7), had little effect on the Ca2+-evoked activation of enzyme. These results suggest that micromolar concentrations of Ca2+ activate the activity of tyrosine hydroxylase probably through a Ca2+-dependent phosphorylation in digitonin-permeabilized adrenal medullary cells although the protein kinase(s) responsible for it still remains to be determined.