Effects of<i> N</i>-acyl glucosamines on GABA uptake activity of GABA transporter 1

HU Jing; FAN Hua; YIN Jian

doi:10.11665/j.issn.1000-5048.20160217

Journal of China Pharmaceutical University > 2016 > 47(2): 228-234. > DOI: 10.11665/j.issn.1000-5048.20160217

HU Jing, FAN Hua, YIN Jian. Effects of N-acyl glucosamines on GABA uptake activity of GABA transporter 1[J]. Journal of China Pharmaceutical University, 2016, 47(2): 228-234. DOI: 10.11665/j.issn.1000-5048.20160217

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Effects of N-acyl glucosamines on GABA uptake activity of GABA transporter 1

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Abstract

In order to screen the inhibitors of GAT1 protein, the effects of synthetic N-acylglucosamines on the GABA uptake activity of GAT1 were examined in the HEK-293 cell model stably expressing GAT1 by performing GABA uptake assay. And since the N-linked oligosaccharides, especially their terminal sialic acid of GAT1 are necessary for the function of GAT1, their effects on the modification of N-glycans of GAT1 were also determined by the quantitative analysis of the sialic acid of GAT1. The results showed that 10 mmol /L 3-O-methyl-N-acetylglucosamine(3-O-Met-GlcNAc)reduced the GABA uptake activity of GAT1 to 53%(P< 0. 01)through inhibiting the sialylation of GAT1(66. 8%). And the GABA uptake activities were decreased to 54%, 63%, 63% and 67%(P< 0. 01), respectively, by the treatments of 10 mmol /L N-propionylglucosamine(GlcNProp), N-hexanoylglucosamine(GlcNHex), N-cycloproylgormylglucosamine(GlcNCyclo)and N-acetamidoacetylglucosamine(GlcNAc-acetamido)through inhibiting N-glycan trimming. These results indicate that the analogues of glucosamines have great potential in the development of inhibitors of GAT1 activity or sialic acid biosynthesis.
- γ-aminobutyric acid(GABA),
- N-glycosylation,
- sialic acid,
- N-acyl glucosamines,
- central nervous system disease

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Effects of N-acyl glucosamines on GABA uptake activity of GABA transporter 1

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