Increasing effects of S-methyl-l-cysteine on the extracellular d-serine concentrations in the rat medial frontal cortex
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In an in vivo dialysis experiment, the intra-medial frontal cortex infusion of a system A and Asc-1 transporter inhibitor, S-methyl-l-cysteine, caused a concentration-dependent increase in the dialysate contents of an endogenous coagonist for the N-methyl-d-aspartate (NMDA) type glutamate receptor, d-serine, in the cortical portion. These results suggest that these neutral amino acid transporters could control the extracellular d-serine signaling in the brain and be a target for the development of a novel threapy for neuropsychiatric disorders with an NMDA receptor dysfunction.
KeywordsAsc-1 transporter In vivo microdialysis Medial frontal cortex S-Methyl-l-cysteine d-Serine
This work was supported by the CREST (Core Research for Evolutional Science and Technology) program funded by the Ministry of Education, Culture, Sports, Science and Technology of Japan.
Conflict of interest
- Fukasawa Y, Segawa H, Kim JY, Chairoungdua A, Kim DK, Matsuo H, Cha SH, Endou H, Kanai Y (2000) Identification and characterization of a Na(+)-independent neutral amino acid transporter that associates with the 4F2 heavy chain and exhibits substrate selectivity for small neutral d- and l-amino acids. J Biol Chem 275(13):9690–9698PubMedCrossRefGoogle Scholar
- Kanematsu S, Ishii S, Umino A, Fujihira T, Kashiwa A, Yamamoto N, Kurumaji A, Nishikawa T (2006) Evidence for involvement of glial cell activity in the control of extracellular d-serine contents in the rat brain. J Neural Transm 113(11):1717–1721. doi: 10.1007/s00702-006-0517-3 PubMedCrossRefGoogle Scholar
- Nishijima K, Kashiwa A, Hashimoto A, Iwama H, Umino A, Nishikawa T (1996) Differential effects of phencyclidine and methamphetamine on dopamine metabolism in rat frontal cortex and striatum as revealed by in vivo dialysis. Synapse 22(4):304–312. doi: 10.1002/(SICI)1098-2396(199604)22:4 PubMedCrossRefGoogle Scholar
- Paxinos G, Watson C (2005) The Rat Brain in stereotaxic coordinates, 5th edn. Elsevier academic press, AmsterdamGoogle Scholar
- Thomsen C, Helboe L, Egebjerg JJ (2003) Use of asc-1 inhibitors to treat neurological and psychiatric disorders. World International Property Organization patent application, WO 2003/077998. http://patentscope.wipo.int/search/en/WO2003077998. Accessed 25 Sept. 2003