BDNF modulates glycine uptake in hippocampal synaptosomes by decreasing membrane insertion of glycine transporter 2

2016 ◽  
Vol 99 ◽  
pp. 94-102 ◽  
Author(s):  
Rita I. Aroeira ◽  
Sandra H. Vaz ◽  
Ana M. Sebastião ◽  
Cláudia A. Valente
Keyword(s):  
Membrane Insertion ◽  
Glycine Uptake ◽  
Glycine Transporter ◽  
Glycine Transporter 2

The neuronal glycine transporter 2 interacts with the PDZ domain protein syntenin-1

2004 ◽  
Vol 26 (4) ◽  
pp. 518-529 ◽  
Author(s):  
Koji Ohno ◽  
Michael Koroll ◽  
Oussama El Far ◽  
Petra Scholze ◽  
Jesus Gomeza ◽  
...  
Keyword(s):  
Pdz Domain ◽  
Glycine Transporter ◽  
Domain Protein ◽  
Glycine Transporter 2

scholarly journals Lidocaine Metabolites Inhibit Glycine Transporter 1

2012 ◽  
Vol 116 (1) ◽  
pp. 147-158 ◽  
Author(s):  
Robert Werdehausen ◽  
David Kremer ◽  
Timo Brandenburger ◽  
Lukas Schlösser ◽  
Janusz Jadasz ◽  
...  
Keyword(s):  
Antinociceptive Effect ◽  
Xenopus Laevis Oocytes ◽  
Glycine Uptake ◽  
Glycine Transporter 1 ◽  
Glycine Transporter ◽  
Glycine Transporters ◽  
Antinociceptive Effects ◽  
Rat Astrocytes ◽  
Induced Currents ◽  
Toxic Concentrations

Background Lidocaine exerts antinociceptive effects when applied systemically. The mechanisms are not fully understood but glycinergic mechanisms might be involved. The synaptic glycine concentration is controlled by glycine transporters. Whereas neurons express two types of glycine transporters, astrocytes specifically express glycine transporter 1 (GlyT1). This study focuses on effects of lidocaine and its major metabolites on GlyT1 function. Methods The effects of lidocaine and its metabolites monoethylglycinexylidide (MEGX), glycinexylidide, and N-ethylglycine on GlyT1 function were investigated in uptake experiments with [¹⁴C]-labeled glycine in primary rat astrocytes. Furthermore, the effect of lidocaine and its metabolites on glycine-induced currents were investigated in GlyT1-expressing Xenopus laevis oocytes. Results Lidocaine reduced glycine uptake only at toxic concentrations. The metabolites MEGX, glycinexylidide, and N-ethylglycine, however, significantly reduced glycine uptake (P < 0.05). Inhibition of glycine uptake by a combination of lidocaine with its metabolites at a clinically relevant concentration was diminished with increasing extracellular glycine concentrations. Detailed analysis revealed that MEGX inhibits GlyT1 function (P < 0.05), whereas N-ethylglycine was identified as an alternative GlyT1 substrate (EC₅₀ = 55 μM). Conclusions Although lidocaine does not function directly on GlyT1, its metabolites MEGX and N-ethylglycine [corrected] were shown to inhibit GlyT1-mediated glycine uptake by at least two different mechanisms. Whereas N-ethylglycine [corrected] was demonstrated to be an alternative GlyT1 substrate, MEGX was shown to inhibit GlyT1 activity in both primary astrocytes and in GlyT1-expressing Xenopuslaevis oocytes at clinically relevant concentrations. These findings provide new insights into the possible mechanisms for the antinociceptive effect of systemic lidocaine.

scholarly journals Spinal Cord Glycine Transporter 2 Mediates Bilateral ST35 Acupoints Sensitization in Rats with Knee Osteoarthritis

2019 ◽  
Vol 2019 ◽  
pp. 1-17 ◽  
Author(s):  
Fuhai Bai ◽  
Yongyuan Ma ◽  
Haiyun Guo ◽  
Yuheng Li ◽  
Feifei Xu ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Mast Cell ◽  
Knee Osteoarthritis ◽  
Dorsal Horn ◽  
Intrathecal Administration ◽  
Mast Cell Degranulation ◽  
Spinal Cord Dorsal Horn ◽  
Glycine Transporter ◽  
Mechanical Threshold ◽  
Glycine Transporter 2

The concept of “acupoint sensitization” refers to the functional status of acupoint switches from silent to active under pathological conditions. In clinic, acupoint sensitization provides important guidance for acupoints selection in different diseases. However, the mechanism behind this phenomenon remains unclear. We generated a model of knee osteoarthritis (KOA) by intra-articular injection of monosodium iodoacetate (MIA) into the left knee of rats. The paw withdrawal mechanical threshold (PWMT) and the total number of mast cells as well as mast cell degranulation rate (MCDR) of acupoint tissue were used to test whether the acupoints were sensitized. The results showed that KOA resulted in a reduced mechanical threshold and elevated total number of mast cell as well as mast cell degranulation rate at bilateral ST35 (Dubi) but not GB37 (Guangming) or nonacupoint area. The acupoint sensitization was accompanied by upregulation of glycine transporter 2 (GlyT2) and reduction of extracellular glycine levels in the bilateral dorsal horns of the spinal cord at L3-5. Selective inhibition of GlyT2 or intrathecal administration of glycine attenuated ST35 acupoint sensitization. The sensitization of bilateral ST35 was blocked after intraspinal GlyT2 short hairpin (sh) RNA (GlyT2-shRNA) microinjection to specifically downregulate GlyT2 expression in the left side (ipsilateral) L3-5 spinal cord dorsal horn before MIA injection. Moreover, electroacupuncture (EA) stimulation at ST35 ameliorated articular pathological lesions and improved KOA-related pain behaviors. GlyT2-shRNA injection reversed EA-induced pain relief but not EA-induced reduction of joint lesions. Overall, this study demonstrated that spinal GlyT2, especially elevated GlyT2 expression in the ipsilateral dorsal horn of the spinal cord, is a crucial mediator of ST35 acupoint sensitization in KOA rats.

scholarly journals Molecular Basis of the Dominant Negative Effect of a Glycine Transporter 2 Mutation Associated with Hyperekplexia

2014 ◽  
Vol 290 (4) ◽  
pp. 2150-2165 ◽  
Author(s):  
Esther Arribas-González ◽  
Jaime de Juan-Sanz ◽  
Carmen Aragón ◽  
Beatriz López-Corcuera
Keyword(s):  
Molecular Basis ◽  
Dominant Negative ◽  
Dominant Negative Effect ◽  
Glycine Transporter ◽  
Negative Effect ◽  
Glycine Transporter 2

scholarly journals A glycine transporter 2-Cre knock-in mouse line for glycinergic neuron-specific gene manipulation

IBRO Reports ◽  
2017 ◽  
Vol 3 ◽  
pp. 9-16 ◽  
Author(s):  
Toshikazu Kakizaki ◽  
Hiroyuki Sakagami ◽  
Kenji Sakimura ◽  
Yuchio Yanagawa
Keyword(s):  
Specific Gene ◽  
Mouse Line ◽  
Gene Manipulation ◽  
Glycine Transporter ◽  
Glycine Transporter 2

The Antinociceptive Effect of Intrathecal Administration of Glycine Transporter-2 Inhibitor ALX1393 in a Rat Acute Pain Model

2010 ◽  
Vol 110 (2) ◽  
pp. 615-621 ◽  
Author(s):  
Yasunori Haranishi ◽  
Koji Hara ◽  
Tadanori Terada ◽  
Seiya Nakamura ◽  
Takeyoshi Sata
Keyword(s):  
Acute Pain ◽  
Antinociceptive Effect ◽  
Intrathecal Administration ◽  
Pain Model ◽  
Glycine Transporter ◽  
Glycine Transporter 2

Neurons expressing GAD 67 and glycine transporter 2 mRNA in and around the trigeminal motor nucleus of the rat

2007 ◽  
Vol 58 ◽  
pp. S91
Author(s):  
Akira Kawata ◽  
Hiroyuki Hayashi ◽  
Hideko Tsuzuki ◽  
Shigehiko Oguri ◽  
Tomohisa Sugiyama ◽  
...  
Keyword(s):  
Motor Nucleus ◽  
Trigeminal Motor Nucleus ◽  
Glycine Transporter ◽  
Glycine Transporter 2

scholarly journals The postnatal development of ultrasonic vocalization‐associated breathing is altered in glycine transporter 2‐deficient mice

2018 ◽  
Vol 597 (1) ◽  
pp. 173-191 ◽  
Author(s):  
Swen Hülsmann ◽  
Yoshihiko Oke ◽  
Guillaume Mesuret ◽  
A. Tobias Latal ◽  
Michal G. Fortuna ◽  
...  
Keyword(s):  
Postnatal Development ◽  
Ultrasonic Vocalization ◽  
Glycine Transporter ◽  
Deficient Mice ◽  
Glycine Transporter 2
Sign in / Sign up

Export Citation Format

Share Document