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Science 22 May 1981:
Vol. 212. no. 4497, pp. 955 - 956
DOI: 10.1126/science.7233193
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Articles

Science, Vol 212, Issue 4497, 955-956
Copyright © 1981 by American Association for the Advancement of Science

articles

Peripherally administered reduced pterins do enter the brain

G Kapatos and S Kaufman

The content of tetrahydrobiopterin in rat brain was doubled by peripherally administered tetrahydrobiopterin, with the natural 1 diastereoisomer more effective than the unnatural d configuration. The model pteridine, 6-methyltetrahydropterin was ten times more efficient than tetrahydrobiopterin in crossing the blood-brain barrier, and striatal concentrations of 6-methyltetrahydropterin remained elevated for 2 hours, declining with a half-life of 3 hours. While no evidence for a specific uptake mechanism for concentrating 6-methyltetrahydropterin in cells containing tetrahydrobiopterin was detected, the pterin was found in ts presumed site of action, the nerve terminal. Replacement therapy with reduced pterins may therefore be effective in the treatment of the neurological disorders associated with the variant forms of hyperphenylalaninemia that result from defects in the biosynthesis or metabolism of tetrahydrobiopterin within the central nervous system.


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Blockade of Tetrahydrobiopterin Synthesis Protects Neurons after Transient Forebrain Ischemia in Rat: A Novel Role for the Cofactor.
S. Cho, B. T. Volpe, Y. Bae, O. Hwang, H. J. Choi, J. Gal, L. C. H. Park, C. K. Chu, J. Du, and T. H. Joh (1999)
J. Neurosci. 19, 878-889
   Abstract »    Full Text »    PDF »
Double Transduction with GTP Cyclohydrolase I and Tyrosine Hydroxylase Is Necessary for Spontaneous Synthesis of L-DOPA by Primary Fibroblasts.
C. Bencsics, S. R. Wachtel, S. Milstien, K. Hatakeyama, J. B. Becker, and U. J. Kang (1996)
J. Neurosci. 16, 4449-4456
   Abstract »    Full Text »    PDF »
Tetrahydrobiopterin in striatum: localization in dopamine nerve terminals and role in catecholamine synthesis.
R. Levine, L. Miller, and W Lovenberg (1981)
Science 214, 919-921
   Abstract »    PDF »


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