Gabapentin and (S)-pregabalin decrease intracellular D-serine concentrations in PC-12 cells

NEUROSCIENCE LETTERS

卷:535

Article

Singh, Nagendra S.¹  Paul, Rajib K.¹  Torjman, Marc C.²  Wainer, Irving W.¹ 

[1] NIA, Lab Clin Invest, NIH, Baltimore, MD 21224 USA

[2] Rowan Univ, Cooper Med Sch, Biostat Grp, Camden, NJ 08103 USA

关键词: D-Serine;    Serine racemase;    Neuropathic pain;    N-Methyl D-aspartate receptor;    Gabapentin;    (S)-pregabalin;   

DOI  :  10.1016/j.neulet.2012.12.024

来源: Elsevier

【 摘 要 】

The effects of gabapentin (GBP) and (S)-pregabalin (PGB) on the intracellular concentrations of D-serine and the expression of serine racemase (SR) in PC-12 cells were determined. Intracellular D-serine concentrations were determined using an enantioselective capillary electrophoresis assay with laser-induced fluorescence detection. Increasing concentrations of GBP, 0.1-20 mu M, produced a significant decrease in D-serine concentration relative to control, 22.9 +/- 6.7% at 20 mu M (*p < 0.05), with an IC50 value of 3.40 +/- 10.29 mu M. Increasing concentrations of PGB, 0.1-10 mu M, produced a significant decrease in D-serine concentration relative to control, 25.3 +/- 17.6% at 10 mu M (*p < 0.05), with an IC50 value of 3.38 +/- 10.21 mu M. The compounds had no effect on the expression of monomeric-SR or dimeric-SR as determined by Western blotting. The results suggest that incubation of PC-12 cells with GBP and PGB reduced the basal activity of SR, which is most likely a result of the decreased Ca2+ flux produced via interaction of the drugs with the alpha(2)-delta subunit of voltage-gated calcium channels. D-Serine is a co-agonist of the N-methyl D-aspartate receptor (NMDAR) and reduced D-serine concentrations have been associated with reduced NMDAR activity. Thus, GBP and PGB may act as indirect antagonists of NMDAR, a mechanism that may contribute to the clinical effects of the drugs in neuropathic pain. Published by Elsevier Ireland Ltd.

【 授权许可】

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