Molecular Pharmacology, Vol 8, 293-299, Copyright © 1972 by the American Society for Pharmacology and Experimental Therapeutics

Studies on the Mechanism of the L-3,4-Dihydroxyphenylalanine-Induced Decrease in Tyrosine Hydroxylase Activity

¹ Roche Institute of Molecular Biology, Nutley, New Jersey 07110

The administration of large amounts of L-3,4-dihydroxyphenylalanine (L-dopa) to rats, guinea pigs, and gerbils decreases the measurable tyrosine hydroxylase activity of adrenal tissues. This effect does not appear to be related to the presence of inhibitory substances in the tissues or a change in the kinetic parameters of the enzyme. The concomitant administration of an aromatic L-amino acid decarboxylase inhibitor, N¹-(DL-seryl)-N²-(2,3,4-trihydroxybenzyl)hydrazine (Ro 4-4602), prevents the L-dopa-mediated decrease in tyrosine hydroxylase activity, thus indicating the necessity for decarboxylation of administered L-dopa to catecholamines. The direct involvement of either the endocrine or sympathetic nervous system in this phenomenon is unlikely, since neither hypophysectomy nor adrenal denervation attenutated the L-dopa-induced decrease of adrenal tyrosine hydroxylase activity.