Aromatic L-amino acid decarboxylase activity of mouse striatum is modulated via dopamine receptors.
Aromatic L-amino acid decarboxylase (AAAD) activity is enhanced in the striatum of control and MPTP-treated mice after administration of a single dose of the dopamine receptor antagonists haloperidol, sulpiride, and SCH 23390. MPTP-treated mice appear more sensitive to the antagonists, i.e., respond earlier and to lower doses of antagonists than control mice. The rise of AAAD activity induced by the antagonists is prevented by pretreatment with cycloheximide. The apparent Km values for L-3,4-dihydroxyphenylalanine (L-DOPA) and pyridoxal 5-phosphate appear unchanged after treatment with the antagonists. Increased AAAD activity was observed also after subchronic administration of dopamine receptor antagonists or treatment with reserpine. A single dose of a selective dopamine receptor agonists had no effect on AAAD activity. In contrast, administration of L-DOPA, quinpirole, or SKF 23390 for 7 days lowers AAAD activity in the striatum. We conclude that AAAD is modulated in striatum via dopaminergic receptors.
Department of Pharmacology, Ohio State University College of Medicine, Columbus 43210-1239.
M
M
Hadjiconstantinou
T A
TA
Wemlinger
C P
CP
Sylvia
J P
JP
Hubble
N H
NH
Neff
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000494:pharmacology*; D000818:Animals; D001142:Aromatic-L-Amino-Acid Decarboxylases / Q000378:metabolism*; D001552:Benzazepines / Q000494:pharmacology*; D001971:Bromocriptine / Q000494:pharmacology; D003342:Corpus Striatum / Q000187:drug effects / Q000201:enzymology*; D003513:Cycloheximide / Q000494:pharmacology; D018492:Dopamine Antagonists; D006220:Haloperidol / Q000494:pharmacology*; D007700:Kinetics; D007980:Levodopa / Q000494:pharmacology; D008297:Male; D051379:Mice; D011732:Pyridoxal Phosphate / Q000494:pharmacology; D011954:Receptors, Dopamine / Q000187:drug effects / Q000502:physiology*; D012110:Reserpine / Q000494:pharmacology; D013469:Sulpiride / Q000494:pharmacology*; D013997:Time Factors
D001552:Benzazepines; D018492:Dopamine Antagonists; D011954:Receptors, Dopamine; D001971:Bromocriptine; D007980:Levodopa; D011732:Pyridoxal Phosphate; D013469:Sulpiride; D012110:Reserpine; D003513:Cycloheximide; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D001142:Aromatic-L-Amino-Acid Decarboxylases; D006220:Haloperidol