Preferred stereoselective brain uptake of d-serine - A modulator of glutamatergic neurotransmission

Dagmar Bauer, Kurt Hamacher, Stefan Bröer, Dirk Pauleit, Christoph Palm, Karl Zilles, Heinz H. Coenen, Karl Josef Langen*

*Corresponding author for this work

    Research output: Contribution to journalArticlepeer-review

    51 Citations (Scopus)

    Abstract

    Although it has long been presumed that d-amino acids are uncommon in mammalians, substantial amounts of free d-serine have been detected in the mammalian brain. d-Serine has been demonstrated to be an important modulator of glutamatergic neurotransmission and acts as an agonist at the strychnine-insensitive glycine site of N-methyl-d-aspartate receptors. The blood-to-brain transfer of d-serine is thought to be extremely low, and it is assumed that d-serine is generated by isomerization of l-serine in the brain. Stimulated by the observation of a preferred transport of the d-isomer of proline at the blood-brain barrier, we investigated the differential uptake of [3H]-d-serine and [3H]-l-serine in the rat brain 1 h after intravenous injection using quantitative autoradiography. Surprisingly, brain uptake of [3H]-d-serine was significantly higher than that of [ 3H]-l-serine, indicating a preferred transport of the d-enantiomer of serine at the blood-brain barrier. This finding indicates that exogenous d-serine may have a direct influence on glutamatergic neurotransmission and associated diseases.

    Original languageEnglish
    Pages (from-to)793-797
    Number of pages5
    JournalNuclear Medicine and Biology
    Volume32
    Issue number8
    DOIs
    Publication statusPublished - Nov 2005

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