Abstract
Tyrosine hydroxylase (tyrosine 3-monoxygenase, EC 1.14.16.2, TH) catalyses the rate limiting step of catecholamine biosynthesis, In vitro, TH from central dopaminergic1–4 as well as from central5,6 and peripheral6,7 noradrenergic neurones can be activated by a cyclic AMP-dependent phosphorylation process and several authors7–9 have proposed that this process can be responsible for the in vivo activation of TH resulting from the electrical stimulation of these neurones. However, this is unlikely to be the case for TH in central dopaminergic neurones because depolarization produces an enzyme activation which is additive with that due to the cyclic AMP-dependent phosphorylation process10–12. In the case of tryptophan hydroxylase in central serotoninergic neurones, recent evidence indicates that a Ca2+-dependent instead of a cyclic AMP-dependent phosphorylation process is responsible for the increased enzyme activity triggered by depolarization13. This finding led us to investigate whether a Ca2+-dependent phosphorylation process also accounts for the activation of TH inside depolarized dopaminergic terminals. We found that soluble TH from the rat striatum could be activated by a Ca2+-dependent process in optimal conditions for producing the phosphorylation of proteins. This activation corresponded exactly to that resulting from the incubation of striatal slices in K+-enriched medium and indeed TH activity from depolarized dopaminergic terminals could not be further stimulated by Ca2+-dependent phosphorylating conditions. In contrast, in situ TH activation by cyclic AMP-dependent phosphorylation (triggered by dibutyryl cyclic AMP or forskolin) did not prevent subsequent stimulation by Ca2+-dependent phosphorylation. These findings suggest that TH activation in depolarized dopaminergic terminals involves a Ca2+-dependent phosphorylation process similar to that controlling tryptophan hydroxylase activity in serotoninergic neurones.
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El Mestikawy, S., Glowinski, J. & Hamon, M. Tyrosine hydroxylase activation in depolarized dopaminergic terminals—involvement of Ca2+ -dependent phosphorylation. Nature 302, 830–832 (1983). https://doi.org/10.1038/302830a0
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DOI: https://doi.org/10.1038/302830a0
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