Glial transport of the neuromodulator D-serine.
D-Serine is an endogenous agonist of NMDA receptors that occurs in astrocytes in gray matter areas of the brain. D-Serine is synthesized from L-serine by the activity of a glial enriched serine racemase, but little is known on the properties of D-serine transport and factors regulating its synaptic concentration. In the present report we characterize the transport of D-serine in astrocytes. In primary astrocyte cultures, D-serine uptake is dependent on sodium ions and exhibits both low affinity and low specificity for D-serine. The kinetics of D-serine transport resembles that of ASCT type transporters as several small neutral amino acids strongly inhibit the uptake of D-serine. D-Serine fluxes are coupled to counter-movement of L-serine and to a less extent to other small neutral amino acids. Thus, addition of D-serine to cell cultures elicits robust efflux of intracellular L-serine. Conversely, physiological concentrations of L-serine induce efflux of preloaded D-serine from astrocytes. L-Serine was more effective than kainate, which have been previously shown to induce D-serine release from astrocytes upon stimulation of non-NMDA type of glutamate receptors. The features of D-serine transport we describe reveal possible new mechanisms controlling the synaptic concentration of D-serine.
Ribeiro
Cátia S
CS
Department of Biochemistry, Federal University of Rio de Janeiro, Rio de Janeiro 21491-590, Brazil.
Reis
Marcelo
M
Panizzutti
Rogério
R
de Miranda
Joari
J
Wolosker
Herman
H
D021542:Amino Acids, Neutral / Q000494:pharmacology; D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D001667:Binding, Competitive; D001692:Biological Transport / Q000187:drug effects; D002352:Carrier Proteins / Q000378:metabolism; D002478:Cells, Cultured; D018690:Excitatory Amino Acid Agonists / Q000493:pharmacokinetics* / Q000494:pharmacology; D007425:Intracellular Membranes / Q000378:metabolism; D007477:Ions; D007700:Kinetics; D018377:Neurotransmitter Agents / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012694:Serine / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology; D012964:Sodium / Q000378:metabolism; D013237:Stereoisomerism
D021542:Amino Acids, Neutral; D002352:Carrier Proteins; D018690:Excitatory Amino Acid Agonists; D007477:Ions; D018377:Neurotransmitter Agents; D012694:Serine; D012964:Sodium