Phorbol ester administration transiently increases aromatic L-amino acid decarboxylase activity of the mouse striatum and midbrain.
Aromatic L-amino acid decarboxylase (AAAD) is required for the synthesis of catecholamines, serotonin, and the trace amines. We found that the protein kinase C activator phorbol 12-myristate 13-acetate administered intracerebroventricularly transiently increased AAAD activity by 30-50% over control values within approximately 30 min in the striatum and midbrain of the mouse. The enzyme increase was manifested as an apparent increase of Vmax with little change of Km for either L-3,4-dihydroxyphenylalanine or pyridoxal phosphate. Chelerythrine, a protein kinase C inhibitor, prevented the phorbol ester-induced increase of AAAD. Moreover, okadaic acid, a serine/threonine-selective protein phosphatase 1 and 2A inhibitor, also increased AAAD activity in the mouse striatum and midbrain. Taken together, these observations suggest that protein kinase C-mediated pathways modulate AAAD activity in vivo.
Department of Pharmacology, Ohio State University College of Medicine, Columbus 43210-1239.
E A
EA
Young
N H
NH
Neff
M
M
Hadjiconstantinou
D000470:Alkaloids; D000818:Animals; D001142:Aromatic-L-Amino-Acid Decarboxylases / Q000378:metabolism*; D053119:Benzophenanthridines; D002552:Cerebral Ventricles / Q000187:drug effects / Q000502:physiology*; D003342:Corpus Striatum / Q000187:drug effects / Q000201:enzymology*; D004988:Ethers, Cyclic / Q000494:pharmacology; D007276:Injections, Intraventricular; D007700:Kinetics; D007980:Levodopa / Q000378:metabolism; D008297:Male; D008636:Mesencephalon / Q000187:drug effects / Q000201:enzymology*; D051379:Mice; D019319:Okadaic Acid; D010617:Phenanthridines / Q000494:pharmacology; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D054645:Protein Phosphatase 1; D011732:Pyridoxal Phosphate / Q000378:metabolism; D012016:Reference Values; D012044:Regression Analysis; D013755:Tetradecanoylphorbol Acetate / Q000008:administration & dosage / Q000494:pharmacology*
D000470:Alkaloids; D053119:Benzophenanthridines; D004988:Ethers, Cyclic; D010617:Phenanthridines; D019319:Okadaic Acid; D007980:Levodopa; D011732:Pyridoxal Phosphate; C016299:chelerythrine; D011493:Protein Kinase C; D010749:Phosphoprotein Phosphatases; D054645:Protein Phosphatase 1; D001142:Aromatic-L-Amino-Acid Decarboxylases; D013755:Tetradecanoylphorbol Acetate