In conclusion we demonstrated that extrasynaptic glutamate c
In conclusion, we demonstrated that extrasynaptic glutamate could in situ affect the AA metabolism via brain CYPs. CYP1B1 and CYP2U1 genes in the astrocytes are the downstream genes of CREB, and the up-regulation of CYP1B1 and CYP2U1 expression by glutamate was due to the increases in phosphorylated CREB proteins in the nuclear and the binding of the CREB protein with the CYP1B1 and CYP2U1 promoters. These data provided the evidence that the neuron-astrocyte reciprocal signaling can change the AA metabolism (e.g. EETs and HETEs) in astrocytes via its specific receptor. The alteration of AA deviates may affect blood flow in the microenvironment within the brain.
Conflict of interest
Acknowledgments This study was supported by the Fundamental Research Funds for the Central Universities, the Program for New Century Excellent Talents in University (NCET-11-0399) and the National Natural Science Foundation of China (No. 30973582 and 81673503).
Introduction γ-aminobutyric GSK1838705A synthesis (GABA) is widely distributed in organisms and acts as a major inhibitory neurotransmitter in mammalian central nervous system . GABA also possesses several other physiological functions, such as anti-depressive, diuretic and anti-oxidant effects [2,3]. Hence, GABA has potential features as a bioactive component in pharmaceuticals and food [4,5]. Many microorganisms including yeasts, Aspergillus species, and lactic acid bacteria have shown GABA-producing ability [4,6,7]. The production of lactic acid bacterial GABA has been gradually garnered favor due to the fact that LAB are generally regarded as safe and have shown relatively high GABA production potential [8,9]. The bio-production of GABA involved a lot of time-consuming, tedious and complicated work, such as screening GABA-producing strains, optimizing GABA fermentation conditions, and monitoring GABA bioconversion processes [, , ]. Several chromatography-based methods including amino acid analyzer , HPLC [, , , ], tandem mass spectrometry  and gas chromatography  have been employed to assay GABA. Nevertheless, these methods require expensive instruments and strict sample pre-treatments. To reduce the workload and cost, it is of great interest to develop an efficient and handy quantitative analysis method for GABA. In organisms, the biotransformation of GABA is based on the decarboxylation of glutamate by glutamic acid decarboxylase. Therefore, the elimination of interference of glutamate is essential for the GABA assay and is one of the major challenges in the approaches regardless of chromatography- or colorimetry-based [9,20,21]. A specific separation column was generally employed to separate GABA from other components in chromatography-based methods [13,16,18,19]. In the colorimetry-based procedures, glutamate was separated from GABA by (pre-staining) paper chromatography ; or the interference of glutamate was indirectly partially removed by the expensive GABase , possibly suffering from insufficient accuracy or reproducibility. However, a colorimetry-based method still has several advantages owing to its economy, simplicity, and high-throughput, in which a convenient and efficient exclusion of glutamate is crucial .
Materials and methods
Results and discussion
Declarations of interest
Acknowledgements This study was financially supported by the National Natural Science Foundation of China (grant Nos 31570070 and 21566023) and Jiangxi Provincial Department of Science and Technology (grant Nos 20171BCB23019 and 20171BAB204002).
Introduction The concept of allosteric receptor–receptor interactions in G protein-coupled receptor (GPCR) homo- and heteroreceptor complexes of the central nervous system (CNS) gave a new biological principle to understanding brain integration and neuropsychopharmacology [, , , , , , , ]. Allosteric receptor–receptor interactions, accomplished through receptor oligomerization, led to novel receptor dynamics during which the receptor protomers change their recognition, pharmacology, signaling and trafficking and novel allosteric binding sites can develop, see also [6,, , ].