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Dopamine Autoreceptors Modulate the Phosphorylation of Tyrosine Hydroxylase in Rat Striatal Slices
Author(s) -
Salah Raymond S.,
Kuhn Donald M.,
Galloway Matthew P.
Publication year - 1989
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1989.tb09202.x
Subject(s) - tyrosine hydroxylase , autoreceptor , tyrosine 3 monooxygenase , dopamine , phosphorylation , chemistry , striatum , tyrosine , neuroscience , medicine , endocrinology , biology , biochemistry , serotonin , receptor
The hypothesis that dopamine (DA) autoreceptors modulate the phosphorylation of tyrosine hydroxylase (TH; EC 1.14.16.2) was investigated in rat striatal slices. Tissue was prelabeled with 32 P inorganic phosphate, and TH recovered by immunoprecipitation with anti‐TH rabbit serum. The TH monomer was resolved on sodium dodecyl sulfate polyacrylamide gels, and the extent of phosphorylation was determined by scanning densitometry of autoradiographs. Depolarization of striatal slices with 55 m M K + markedly increased the incorporation of 32 P into several proteins, including the TH monomer (M r = 60,000). A similar increase in TH phosphorylation occurred in response to the adenylate cyclase activator forskolin and the cyclic AMP analog dibutyryl cyclic AMP. An increase in TH phosphorylation was not observed in response to the D 1 ‐selective agonist SKF 38393. The D 2 ‐selective DA autoreceptor agonist pergolide decreased the phosphorylation of TH below basal levels and blocked the increase in phosphorylation elicited by 55 m M K + . The inhibitory effect of pergolide was antagonized by the D 2 ‐selective antagonist eticlopride. Changes observed in the phosphorylation of TH were mirrored by changes in tyrosine hydroxylation in situ. These observations support the hypothesis that a reduction in TH phosphorylation is the mechanism by which DA autoreceptors modulate tyrosine hydroxylation in nigrostriatal nerve terminals.