REDUCTION IN THE LEVEL OF IMMUNO-TITRATABLE DOPAMINE BETA-HYDROXYLASE AFTER CHRONIC ADMINISTRATION OF L-DOPA OR ALPHA-METHYLDOPA

The effect of chronic administration for 7 days of l-DOPA (l.0g/kg/day) or l-α-methyldopa (0.4 g/kg/day) on the activity of dopamine β-hydroxylase in rat adrenal glands and heart was studied. Both drugs reduced adrenal dopamine β-hydroxylase activity by 35%, whereas only α-methyldopa administration lowered enzyme activity in the heart. The reductions were not due to the presence of substances inhibiting enzyme activity. Immunotitration of rat adrenal supernatants with a specific antibody raised to dopamine β-hydroxylase purified from bovine adrenal medulla showed that the reductions in adrenal enzyme activity following l-DOPA and α-methyldopa were due to decreases in the amount of dopamine β-hydroxylase protein. It is unlikely that these reductions in enzyme protein represent a generalized reduction in protein turnover as chronic administration of l-DOPA did not alter the turnover of trichloracetic acid-precipitable soluble protein in adrenals or the heart. Chronic administration of l-DOPA also reduced tyrosine hydroxylase activity in adrenals and the heart and aromatic l-amino acid decarboxylase activity in the heart only. In contrast, heart tyrosine hydroxylase activity was slightly elevated by chronic administration of α-methyldopa, but this dosage regimen considerably reduced both adrenal and heart aromatic l-amino acid decarboxylase activity and slightly decreased the activity of the cytoplasmic marker, lactate dehydrogenase, in adrenal glands. The results are consistent with previous proposals that catecholamine levels may contribute to the regulation of the total amount of dopamine β-hydroxylase in the peripheral nervous system and that the amounts of catecholamine synthesizing and degradative enzymes are regulated in response to transmitter demand. © 1979.