Molecular Pharmacology, Vol 15, 86-98, Copyright © 1979 by the American Society for Pharmacology and Experimental Therapeutics

Reduction of Aromatic L-Amino Acid Decarboxylase Protein in Rats after Chronic Administration of Alpha-Methyldopa

¹ Unit of Clinical Pharmacology and Therapeutics, University of Melbourne, Austin Hospital, Heidelberg, Victoria 3084, Australia

The effect of chronic administration of -methyldopa (400 mg/kg per day for seven days) to rats on the activity and amount of aromatic L-amino acid decarboxylase (EC 4.1.1.28) was studied. Aromatic L-amino acid decarboxylase activity measured in dialyzed supernatants was substantially reduced relative to control levels in all tissues analyzed. This effect was not due to the presence of substances inhibiting enzyme activity or to an alteration in the affinity of aromatic L-amino acid decarboxylase for its substrate, L-dopa. The amount of aromatic L-amino acid decarboxylase in dialyzed supernatants was estimated by immunotitration with a specific antibody raised to the enzyme purified from hog kidney cortex. Chronic administration of -methyldopa caused a substantial decrease in the amount of aromatic L-amino acid decarboxylase protein in all tissues. The extent of the reduction in enzyme activity and enzyme protein was very similar within each tissue. The turnover of total soluble protein, measured by double isotope incorporation, was not altered in heart, brain or liver after -methyldopa administration, although small reductions in adrenal and kidney soluble protein turnover were detected. Potential mechanisms for the reduction of aromatic L-amino acid decarboxylase levels are discussed.