Modulation of tyrosine hydroxylase and aromatic L-amino acid decarboxylase after inhibiting monoamine oxidase-A.
After acute administration of the monoamine oxidase inhibitor clorgyline there is a reduction of aromatic L-amino acid decarboxylase and tyrosine hydroxylase activity in the mouse striatum. Similar responses were seen after administering the non-selective monoamine oxidase inhibitor pargyline and high, but not low, doses of the selective monoamine oxidase-B inhibitor deprenyl. Changes of tyrosine hydroxylase activity were observed only when subsaturated concentrations of the pteridine cofactor were used for the assay. The monoamine oxidase inhibitors altered the abundance of aromatic L-amino acid decarboxylase and tyrosine hydroxylase mRNA in the midbrain. Pargyline and high doses of deprenyl increased, aromatic L-amino acid decarboxylase mRNA, while clorgyline initially decreased and then increased it. All three compounds caused an early decrease of tyrosine hydroxylase mRNA. The acidic metabolites of dopamine appeared most affected by pargyline and clorgyline, supporting the notion that deamination of striatal dopamine in rodents is primarily by monoamine oxidase-A. Our results suggest, that striatal tyrosine hydroxylase and aromatic L-amino acid decarboxylase are apparently modulated via different mechanisms in response to perturbation of dopamine metabolism.
Cho
S
S
Department of Pharmacology, Ohio State University, 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*; D001921:Brain / Q000187:drug effects* / Q000201:enzymology*; D003010:Clorgyline / Q000494:pharmacology; D008297:Male; D051379:Mice; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D012642:Selegiline / Q000494:pharmacology; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism*
D008996:Monoamine Oxidase Inhibitors; D012642:Selegiline; D014446:Tyrosine 3-Monooxygenase; D001142:Aromatic-L-Amino-Acid Decarboxylases; D003010:Clorgyline