Preferred stereoselective brain uptake of d-serine--a modulator of glutamatergic neurotransmission.
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.
Bauer
Dagmar
D
Institute of Medicine, Research Center Jülich, D-52425 Jülich, Germany.
Hamacher
Kurt
K
Bröer
Stefan
S
Pauleit
Dirk
D
Palm
Christoph
C
Zilles
Karl
K
Coenen
Heinz H
HH
Langen
Karl-Josef
KJ
D000818:Animals; D001812:Blood-Brain Barrier / Q000000981:diagnostic imaging / Q000378:metabolism; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism*; D001923:Brain Chemistry; D003903:Deuterium / Q000493:pharmacokinetics; D005973:Glutamine / Q000378:metabolism*; D008297:Male; D008657:Metabolic Clearance Rate; D018377:Neurotransmitter Agents / Q000378:metabolism*; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D051381:Rats; D011916:Rats, Inbred F344; D012694:Serine / Q000493:pharmacokinetics*; D013237:Stereoisomerism; D009435:Synaptic Transmission / Q000502:physiology*; D014018:Tissue Distribution
D018377:Neurotransmitter Agents; D019275:Radiopharmaceuticals; D005973:Glutamine; D012694:Serine; D003903:Deuterium