期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：1971
卷号：68
期号：9
页码：2117-2120
DOI：10.1073/pnas.68.9.2117
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：L-Dopa, an intermediate in the biosynthesis of catecholamines, is now widely used in the treatment of parkinsonism. A number of clinical observations suggested that L-dopa may induce changes in its own metabolism during the course of therapy. In the present study, it was found that when L-dopa was administered to rats, the activity of liver aromatic L-amino-acid decarboxylase, the enzyme which catalyzes the conversion of dopa to dopamine, was reduced by as much as 50%. There were no corresponding changes in enzyme activity in heart, adrenals, kidneys, and brain. Decarboxylase activity in the liver continued to decrease for at least 5 days after the last dose of L-dopa. The reduction of enzyme activity in the liver occurred when L-dopa was administered either subcutaneously or orally at doses comparable to those used clinically. In vitro and in vivo experiments indicated that this action of L-dopa is not due to some effect on the cofactor, pyridoxal phosphate. Immunological evidence was obtained that enzyme protein is reduced in the same proportion as enzyme activity. By a reduction of decarboxylase activity in liver without any affect on the enzyme in brain, more L-dopa should be made available to the brain for decarboxylation to dopamine. These findings may explain the clinical observations that the therapeutic efficacy of the drug increases with continued administration.
