Distribution and pharmacology of alanine-serine-cysteine transporter 1 (asc-1) in rodent brain

Eur J Neurosci. 2003 Oct;18(8):2227-38. doi: 10.1046/j.1460-9568.2003.02966.x.


A polyclonal antibody against the Na+-independent alanine-serine-cysteine transporter 1 (asc-1) was raised and the specificity of the antibody verified by Western blots performed on membranes prepared from HEK293 cells transiently transfected with the cloned murine asc-1. The antibody was then used to localize the transporter in the brain of two rodent species by using immunohistochemistry at the light and electron microscopical level. asc-1-immunoreactivity (asc-1-ir) was widely distributed throughout the mouse and rat brain. Areas with high levels of asc-1-ir included hypothalamus, the medial septal area, globus pallidus, entopeduncular nucleus, cingulate and retrosplenial cortices. Moderate asc-1-ir was observed in several areas including layers III and V of the neocortex, thalamus, nucleus accumbens, caudate putamen, bed nucleus of stria terminalis, all amygdaloid nuclei, hippocampus (CA1-CA3 and hilus of the dentate gyrus), as well as several brainstem nuclei. asc-1-ir was observed as punctuate staining consistent with varicosities matching neuronal cell bodies and dendritic fields. At the ultrastructural level, asc-1-ir was mainly confined to presynaptic terminals. Immunostaining in either glial cell bodies or perivascular sites was not observed and white matter was completely devoid of asc-1-ir. Furthermore, the pharmacology of the Na+-independent uptake site for [3H]d-serine in rat brain synaptosomal P2 fractions was compared with the substrate specificity of the cloned human asc-1 transporter and a high degree of correlation was demonstrated. We conclude that asc-1-ir is widespread in the brain and limited to neuronal structures and that asc-1 may contribute to synaptic clearance of d-serine in brain.

Publication types

  • Comparative Study

MeSH terms

  • Alanine / metabolism
  • Alanine / pharmacology
  • Amino Acid Transport System A / antagonists & inhibitors
  • Amino Acid Transport System ASC / antagonists & inhibitors
  • Amino Acid Transport System L / antagonists & inhibitors
  • Amino Acid Transport System y+ / antagonists & inhibitors
  • Amino Acid Transport System y+ / genetics
  • Amino Acid Transport System y+ / immunology
  • Amino Acid Transport System y+ / metabolism*
  • Animals
  • Blotting, Western
  • Brain / metabolism*
  • Brain / ultrastructure
  • Brain Chemistry
  • Cell Line
  • Cysteine / metabolism
  • Dose-Response Relationship, Drug
  • Embryo, Mammalian
  • Fusion Regulatory Protein-1 / genetics
  • Fusion Regulatory Protein-1 / metabolism
  • Glycine / pharmacology
  • Humans
  • Immunohistochemistry / methods
  • Kidney
  • Male
  • Mice
  • RNA, Messenger / biosynthesis
  • Rats
  • Rats, Wistar
  • Reverse Transcriptase Polymerase Chain Reaction
  • Serine / metabolism
  • Serine / pharmacology
  • Sodium / metabolism
  • Sodium / pharmacology
  • Synaptosomes / metabolism
  • Synaptosomes / ultrastructure
  • Transfection
  • beta-Alanine / analogs & derivatives*
  • beta-Alanine / pharmacology


  • Amino Acid Transport System A
  • Amino Acid Transport System ASC
  • Amino Acid Transport System L
  • Amino Acid Transport System y+
  • Fusion Regulatory Protein-1
  • RNA, Messenger
  • SLC7A10 protein, human
  • Slc7a10 protein, mouse
  • Slc7a10 protein, rat
  • beta-Alanine
  • 2,2-dimethyl-beta-alanine
  • Serine
  • Sodium
  • Cysteine
  • Alanine
  • Glycine