Parallel modulation of striatal dopamine synthetic enzymes by second messenger pathways.
The activity of tyrosine hydroxylase and aromatic L-amino acid decarboxylase in the striatum and their mRNA content in the midbrain were assayed in mice following the intracerebroventricular injection of forskolin or phorbol-12,13-myristic acid (PMA). Control and 1-methyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned animals were studied. Both forskolin and PMA induced a rapid and transient increase of tyrosine hydroxylase and aromatic L-amino acid decarboxylase activity in the striatum that lasted less than 45 and 60 min, respectively. A second belated increase of striatal tyrosine hydroxylase and aromatic L-amino acid decarboxylase activities was seen only after forskolin, and it was accompanied by a rise of tyrosine hydroxylase and aromatic L-amino acid decarboxylase mRNA in the midbrain. In the MPTP-lesioned mouse, the rise of tyrosine hydroxylase and aromatic L-amino acid decarboxylase following forskolin appeared exaggerated, while the response to PMA was not. These studies suggest that tyrosine hydroxylase and aromatic L-amino acid decarboxylase of striatum can be modulated in parallel by protein kinase A and protein kinase C, and that exaggerated responsiveness to protein kinase A is observed in the partially denervated striatum.
Young
E A
EA
Neuroscience Program, Ohio State College of Medicine, Columbus 43210, USA.
Duchemin
A M
AM
Neff
N H
NH
Hadjiconstantinou
M
M
D000818:Animals; D001142:Aromatic-L-Amino-Acid Decarboxylases / Q000378:metabolism*; D002273:Carcinogens / Q000008:administration & dosage / Q000494:pharmacology*; D005576:Colforsin / Q000008:administration & dosage / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism*; D015259:Dopamine Agents / Q000633:toxicity; D007276:Injections, Intraventricular; D020267:MPTP Poisoning; D008297:Male; D008636:Mesencephalon / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D051379:Mice; D015290:Second Messenger Systems / Q000187:drug effects*; D013755:Tetradecanoylphorbol Acetate / Q000008:administration & dosage / Q000494:pharmacology*; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism*
D002273:Carcinogens; D015259:Dopamine Agents; D005576:Colforsin; D014446:Tyrosine 3-Monooxygenase; D001142:Aromatic-L-Amino-Acid Decarboxylases; D013755:Tetradecanoylphorbol Acetate; D004298:Dopamine