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IN VIVO INHIBITION OF RAT BRAIN PROTEIN SYNTHESIS BY l ‐DOPA
Author(s) -
Roel L. E.,
Schwartz S. A.,
Weiss B. F.,
Munro H. N.,
Wurtman R. J.
Publication year - 1974
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1974.tb06939.x
Subject(s) - in vivo , leucine , amino acid , lysine , protein biosynthesis , polysome , alanine , metabolism , protein metabolism , phenylalanine , chemistry , biochemistry , pharmacology , biology , rna , ribosome , microbiology and biotechnology , gene
— A study has been made of the effect of a single intraperitoneal dose of l ‐DOPA on the in vivo metabolism of [ 14 C]leucine and [ 14 C]lysine by the brain, and on their uptake into brain protein. Administration of 500 mg DOPA/kg to 40‐g rats raised the concentrations of several free amino acids; the only amino acid which underwent a statistically significant increment was alanine. Intracisternally‐injected [U‐ 14 C]leucine was rapidly metabolized to other labelled compounds; DOPA administration did not influence significantly the rate of its metabolism. No similar metabolic change was observed after administering [U‐ 14 C]lysine intracisternally. Incorporation of [ 14 C]leucine and [ 14 C]lysine into total brain protein was significantly reduced 45 min after DOPA administration. There was also depression of the uptake of labelled amino acid into a supernatant fraction, obtained by high speed centrifugation of the brain homogenate, and into brain microtubular protein (tubulin). Reduced amino‐acid incorporation into brain proteins observed 45 min after l ‐DOPA injection coincided with extensive disaggregation of brain polyribosomes. At 120 min after DOPA treatment, disaggregation was no longer significant and there was a smaller depression in labelled amino aicd incorporation, which disappeared completely 240 min after l ‐DOPA injection. It is concluded that disaggregation of brain polysomes following DOPA treatment is an accurate reflection of a change in the intensity of brain protein synthesis in vivo.