Increasing effects of S-methyl-l-cysteine on the extracellular d-serine concentrations in the rat medial frontal cortex

Abstract

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.

A novel Na+‐Independent alanine‐serine‐cysteine transporter 1 inhibitor inhibits both influx and efflux of D‐Serine

“…Therefore, whether asc-1 inhibitor results in upregulation or downregulation of extracellular D-ser levels may be affected by equilibration determined by intracellular and extracellular levels. Inhibition of asc-1 by SMLC in the brain is considered to increase the extracellular D-Ser levels according to microdialysis analyses Ishiwata et al, 2013). We replicated SMLC increase of the extracellular D-Ser levels in the rat ventral hippocampus in a concentration-dependent manner (Fig.…”

“…SMLC and ACPP were infused locally into the ventral hippocampus via a dialysis probe, and the D‐Ser levels in the collected dialysate were determined by HPLC. As reported previously (Thomson et al, ; Ishiwata et al, ), SMLC significantly increased the extracellular D‐Ser levels up to approximately 150% of the baseline levels in a concentration‐dependent manner (n = 6) relative to vehicle treatment (n = 6, P < 0.025; Fig. A,C), as revealed by Williams' test.…”

“…Inhibition of asc‐1 by SMLC in the brain is considered to increase the extracellular D‐Ser levels according to microdialysis analyses (Thomsen et al, ; Ishiwata et al, ). We replicated SMLC increase of the extracellular D‐Ser levels in the rat ventral hippocampus in a concentration‐dependent manner (Fig.…”

“…It has been reported that S‐methyl‐L‐cysteine (SMLC), an asc‐1 inhibitor patented by Lundbeck (Deerfield, IL; patent No. WO2003077998A1), inhibits D‐Ser uptake in human asc‐1‐expressing HEK293 cells as well as increasing the extracellular D‐Ser levels in the rat ventral hippocampus and medial prefrontal cortex (Thomsen et al, ; Ishiwata et al, ), which suggests that asc‐1 inhibition can increase the extracellular D‐Ser levels in the brain. Recently, Sason et al () reported that a novel asc‐1 inhibitor, Lu AE00527, decreased the release of D‐Ser from rat brain slices and inhibited long‐term potentiation (LTP), suggesting that asc‐1 mediates tonic D‐Ser release.…”

Neuronal serine racemase regulates extracellular d-serine levels in the adult mouse hippocampus

“…The in vivo microdialysis was performed as previously depicted with some modifications (Ishiwata et al 2013a, b). A straight cellulose dialysis tube (1.0 mm in length, 0.16 mm internal diameter, molecular weight cutoff 50,000, EICOM Co., Ltd., Japan) was implanted into the hippocampus ( A −2.2 mm, V 1.5 mm, L 1.3 mm) according to the atlas of Paxinos and Franklin (2004) on a stereotaxic frame under pentobarbital anesthesia (40 mg/kg, intraperitoneally).…”