Reference

Characterization of 5,7-dichlorokynurenate-insensitive D-[3H]serine binding to synaptosomal fraction isolated from rat brain tissues

Characterization of 5,7-dichlorokynurenate-insensitive D-[3H]serine binding to synaptosomal fraction isolated from rat brain tissues. Matoba, Masaki; Tomita, Urara; Nishikawa, Toru (Department of Mental Disorder Research, National Center of Neurology and Psychiatry, National Institute of Neuroscience, Tokyo 187, Japan). Journal of Neurochemistry, 69(1), 399-405 (English) 1997 Lippincott-Raven. CODEN: JONRA9. ISSN: 0022-3042. DOCUMENT TYPE: Journal CA Section: 13 (Mammalian Biochemistry) To explore target sites for endogenous D-serine that are different from the glycine site of the N-methyl-D-aspartate (NMDA) type glutamate receptor, we have studied the binding of D-[3H]serine to the synaptosomal P2 fraction prepd. from the rat brain and peripheral tissues in the presence of an excess concn. (100 mM) of the glycine site antagonist 5,7-dichlorokynurenate (DCK). Nonspecific binding was defined in the presence of 1 mM unlabeled D-serine. Assocn., dissocn., and satn. expts. indicated that D-[3H]serine bound rapidly and reversibly to a single population of recognition sites in the cerebellar P2 fraction in the presence of DCK, with a KD of 614 nM and a Bmax of 2.07 pmol/mg of protein. D-Serine, L-serine, and glycine produced a total inhibition of the specific DCK-insensitive D-[3H]serine binding to the cerebellum with similar K1 values. Strychnine and 7-chlorokynurenate failed to inhibit the binding at 10 mM. The profiles of displacement of the DCK-insensitive D-[3H]serine binding by various amino acids and glutamate and glycine receptor-related compds. differ from those of any other defined recognition sites. DCK-insensitive D-[3H]serine binding was at high levels in the cerebral cortex and cerebellum but very low in the kidney and liver. The present findings indicate that the DCK-insensitive D-[3H]serine binding site could be a novel candidate for a target for endogenous D-serine in mammalian brains.

Inhibition of D-serine accumulation in the Xenopus oocyte by expression of the rat ortholog of human 3'-phosphoadenosine 5'-phosphosulfate transporter gene isolated from the neocortex as D-serine modulator-1

Inhibition of D-serine accumulation in the Xenopus oocyte by expression of the rat ortholog of human 3'-phosphoadenosine 5'-phosphosulfate transporter gene isolated from the neocortex as D-serine modulator-1. Shimazu, Dai; Yamamoto, Naoki; Umino, Asami; Ishii, Sumikazu; Sakurai, Shin-ichiro; Nishikawa, Toru (Section of Psychiatry and Behavioral Sciences, Tokyo Medical and Dental University Graduate School, Tokyo, Japan). Journal of Neurochemistry, 96(1), 30-42 (English) 2006 Blackwell Publishing Ltd. CODEN: JONRA9. ISSN: 0022-3042. DOCUMENT TYPE: Journal CA Section: 13 (Mammalian Biochemistry) Section cross-reference(s): 3, 6 D-Serine in mammalian brains has been suggested to be an endogenous co-agonist of the NMDA-type glutamate receptor. We have explored the mols. regulating D-serine uptake and release from the rat neocortex cDNA library using a Xenopus oocyte expression system, and isolated a cDNA clone designated as dsm-1 (D-serine modulator-1) encoding a protein that reduces the accumulation of D-serine to the oocyte. Dsm-1 is the rat orthologue of the human 3'-phosphoadenosine 5'-phosphosulfate transporter 1 (PAPST1) gene. The hydropathy anal. of the deduced amino acid sequence of the Dsm-1 protein predicts the 10 transmembrane domains with a long hydrophobic stretch in the C-terminal like some amino acid transporters. The dsm-1 mRNA is predominantly expressed in the forebrain areas that are enriched with D-serine and NMDA receptors, and in the liver. The transient expression of dsm-1 in COS-7 cells demonstrates a partially Golgi app.-related punctuate distribution throughout the cytoplasm with a concn. near the nucleus. Dsm-1-expressing oocytes diminishes the sodium-dependent and -independent accumulation of D-serine and the basal levels of the intrinsic D-serine and increases the rate of release of the pre-loaded D-serine. These findings indicate that dsm-1 may, at least in part, be involved in the D-serine translocation across the vesicular or plasma membranes in the brain, and thereby control the extra- and intracellular contents of D-serine.