Gelsemine and koumine, principal active ingredients of Gelsemium, exhibit mechanical antiallodynia via spinal glycine receptor activation-induced allopregnanolone biosynthesis

2019 ◽  
Vol 161 ◽  
pp. 136-148 ◽  
Author(s):  
Rana Muhammad Shoaib ◽  
Jing-Yang Zhang ◽  
Xiao-Fang Mao ◽  
Yong-Xiang Wang
Keyword(s):  
Glycine Receptor ◽  
Receptor Activation ◽  
Active Ingredients

scholarly journals Nonsynaptic Glycine Receptor Activation during Early Neocortical Development

Neuron ◽  
1998 ◽  
Vol 20 (1) ◽  
pp. 43-53 ◽  
Author(s):  
Alexander C Flint ◽  
Xiaolin Liu ◽  
Arnold R Kriegstein
Keyword(s):  
Glycine Receptor ◽  
Receptor Activation ◽  
Neocortical Development

A glycine receptor antagonist, strychnine, blocked NMDA receptor activation in the neonatal mouse neocortex

Neuroreport ◽  
2002 ◽  
Vol 13 (13) ◽  
pp. 1667-1673 ◽  
Author(s):  
Naohisa Miyakawa ◽  
Shigeo Uchino ◽  
Takayuki Yamashita ◽  
Hidetsugu Okada ◽  
Takeshi Nakamura ◽  
...  
Keyword(s):  
Nmda Receptor ◽  
Receptor Antagonist ◽  
Glycine Receptor ◽  
Receptor Activation ◽  
Neonatal Mouse ◽  
Nmda Receptor Activation

scholarly journals Remote ischemic conditioning provides humoural cross-species cardioprotection through glycine receptor activation

2017 ◽  
Vol 113 (1) ◽  
pp. 52-60 ◽  
Author(s):  
Juan José Alburquerque-Béjar ◽  
Ignasi Barba ◽  
Laura Valls-Lacalle ◽  
Marisol Ruiz-Meana ◽  
Michela Pecoraro ◽  
...  
Keyword(s):  
Glycine Receptor ◽  
Receptor Activation ◽  
Remote Ischemic Conditioning ◽  
Ischemic Conditioning

scholarly journals Glycine transporter-1 antagonist provides 1 neuroprotection in vivo

2021 ◽  
Author(s):  
Richard Bergeron ◽  
Julia Cappelli ◽  
Pamela Khacho ◽  
Boyang Wang ◽  
Alexandra Sokolovski ◽  
...  
Keyword(s):  
Cell Death ◽  
Glycine Receptor ◽  
Synaptic Cleft ◽  
Receptor Activation ◽  
Excitatory Transmission ◽  
Glycine Transporter ◽  
Show Evidence ◽  
High Doses

Abstract Glycine fulfills several roles in biology including protein synthesis, inhibitory transmission via glycine receptor activation and excitatory transmission through glutamate-sensitive N-methyl-D-aspartate receptors (NMDARs). Low glycine doses enhance NMDAR function while high doses trigger glycine-induced NMDAR internalization (GINI) in vitro. The physiological relevance of GINI has been questioned given that the high-affinity glycine transporter type 1 (GlyT1), located on astrocytes and neurons, maintains synaptic glycine concentrations far below the level that would saturate the glycine binding site (GBS) on NMDARs. Here, we report evidence that GINI occurs also in vivo and is neuroprotective following ischemic insult. Mice pre-treated with a GlyT1 antagonist (GlyT1-A), which increased glycine levels, exhibited smaller stroke volume, reduced cell death, and minimized behavioural deficits following stroke induction by either photothrombosis or endothelin-1. We demonstrate that in a modified in vitro ischemic paradigm, glycine is released at levels surpassing what occurs during ischemia alone. Therefore, glycine accumulates in the synaptic cleft, enhances occupancy of GBS and reaches the set point to trigger GINI. We report that GINI is observed during stroke, in vivo, only in the presence of a GlyT1-A. Moreover, we show evidence of a protective effect on the vasculature in the peri-infarct area. Therefore, these data strongly suggest that GlyT1 is a therapeutic target to prevent cell death following an ischemic event.

scholarly journals Conformational Variability of the Glycine Receptor M2 Domain in Response to Activation by Different Agonists

2007 ◽  
Vol 282 (49) ◽  
pp. 36057-36067 ◽  
Author(s):  
Stephan A. Pless ◽  
Mohammed I. Dibas ◽  
Henry A. Lester ◽  
Joseph W. Lynch
Keyword(s):  
Conformational Changes ◽  
Structural Changes ◽  
Glycine Receptor ◽  
Blue Shift ◽  
Receptor Activation ◽  
Emission Peak ◽  
Competitive Antagonist ◽  
Conformational Variability ◽  
Fluorescence Change ◽  
Pore Lining

Models describing the structural changes mediating Cys loop receptor activation generally give little attention to the possibility that different agonists may promote activation via distinct M2 pore-lining domain structural rearrangements. We investigated this question by comparing the effects of different ligands on the conformation of the external portion of the homomeric α1 glycine receptor M2 domain. Conformational flexibility was assessed by tethering a rhodamine fluorophore to cysteines introduced at the 19′ or 22′ positions and monitoring fluorescence and current changes during channel activation. During glycine activation, fluorescence of the label attached to R19′C increased by ∼20%, and the emission peak shifted to lower wavelengths, consistent with a more hydrophobic fluorophore environment. In contrast, ivermectin activated the receptors without producing a fluorescence change. Although taurine and β-alanine were weak partial agonists at the α1R19′C glycine receptor, they induced large fluorescence changes. Propofol, which drastically enhanced these currents, did not induce a glycine-like blue shift in the spectral emission peak. The inhibitors strychnine and picrotoxin elicited fluorescence and current changes as expected for a competitive antagonist and an open channel blocker, respectively. Glycine and taurine (or β-alanine) also produced an increase and a decrease, respectively, in the fluorescence of a label attached to the nearby L22′C residue. Thus, results from two separate labeled residues support the conclusion that the glycine receptor M2 domain responds with distinct conformational changes to activation by different agonists.

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