scholarly journals Acute Administration of Desformylflustrabromine Relieves Chemically Induced Pain in CD-1 Mice

Molecules ◽  
2019 ◽  
Vol 24 (5) ◽  
pp. 944 ◽  
Author(s):  
Loni Weggel ◽  
Anshul Pandya
Keyword(s):  
Nicotinic Acetylcholine Receptors ◽  
Acetylcholine Receptors ◽  
Acute Administration ◽  
Allosteric Modulators ◽  
Neuronal Nicotinic Acetylcholine Receptors ◽  
Nicotinic Acetylcholine ◽  
Chemically Induced ◽  
The Central Nervous System ◽  
Membrane Bound ◽  
Pain Test

Neuronal nicotinic acetylcholine receptors are cell membrane-bound ion channels that are widely distributed in the central nervous system. The α4β2 subtype of neuronal nicotinic acetylcholine receptor plays an important role in modulating the signaling pathways for pain. Previous studies have shown that agonists, partial agonists, and positive allosteric modulators for the α4β2 receptors are effective in relieving pain. Desformylflustrabromine is a compound that acts as an allosteric modulator of α4β2 receptors. The aim of this study was to assess the effects of desformylflustrabromine on chemically induced pain. For this purpose, the formalin-induced pain test and the acetic acid-induced writhing response test were carried out in CD-1 mice. Both tests represent chemical assays for nociception. The results show that desformylflustrabromine is effective in producing an analgesic effect in both tests used for assessing nociception. These results suggest that desformylflustrabromine has the potential to become a clinically used drug for pain relief.

scholarly journals In Silico Analysis of Ethanol Binding Activity in Neuronal Nicotinic Acetylcholine Receptors

2020 ◽  
Vol 5 (1) ◽  
pp. 54-61
Author(s):  
Angganararas Lungidningtyas ◽  
Arli Aditya Parikesit
Keyword(s):  
Nicotinic Acetylcholine Receptors ◽  
Acetylcholine Receptors ◽  
Specific Binding ◽  
In Silico Analysis ◽  
Data Bank ◽  
Binding Activity ◽  
Neuronal Nicotinic Acetylcholine Receptors ◽  
Nicotinic Acetylcholine ◽  
The Central Nervous System ◽  
Silico Analysis

Ethanol and nicotine are two common substances that are often linked to complications in alcoholic smokers. The high number of the co-consumptions in alcoholic smokers suggested a possible interaction between ethanol and nicotine in the central nervous system and a potential similar mechanism of action. Both ethanol and nicotine are shown to bind with neuronal nicotinic acetylcholine receptors (nAChRs), a ligand gated cation channel specifically targeted by the endogenous acetylcholine. Ethanol has a much less specific binding capability to modulate the receptors, however, emerging reports indicates that ethanol can interact with nAChRs both directly and indirectly. This study focuses on the analysis of ethanol binding sites with nAChRs using molecular docking techniques obtained from the Protein Data Bank. The obtained data showed a possible binding site for ethanol in nAChRs, however, upon validation, result is not substantial. Nevertheless, the obtained data should be useful for future reference for the basis of ethanol interactions with the human nAChRs proteins.

scholarly journals The possible contribution of neuronal nicotinic acetylcholine receptors in depression

2005 ◽  
Vol 7 (3) ◽  
pp. 207-216 ◽  
Keyword(s):  
Central Nervous System ◽  
Nicotinic Acetylcholine Receptors ◽  
Acetylcholine Receptors ◽  
Neuronal Nicotinic Acetylcholine Receptors ◽  
Cholinergic Transmission ◽  
Nicotinic Acetylcholine ◽  
Addictive Substance ◽  
Treatment Of Depression ◽  
The Central Nervous System ◽  
The Many

Although tobacco use and smoking were introduced long ago, it was only recently that the nicotine contained in the tobacco leaves was recognized as an addictive substance acting on the central nervous system (CNS). However, even prior to this recognition, several studies have reported an association between smoking and psychiatric disorders. One of the many observations was that smoking cessation is accompanied by a marked increase in the probability of major depression. In parallel with the discovery of the neuronal nicotinic acetylcholine receptors and their extensive expression in the CNS, this association sheds new light on the influence of cholinergic transmission in depression. In this article, we examine the various modes of action of nicotine in the CNS and discuss the mechanisms by which this alkaloid can prevent or precipitate mood disorders, and the possibility of discovering new therapeutic avenues for the treatment of depression.

Potentiation and inhibition of subtypes of neuronal nicotinic acetylcholine receptors by Pb2+

1995 ◽  
Vol 291 (3) ◽  
pp. 399-406 ◽  
Author(s):  
Ruud Zwart ◽  
Regina G.D.M. Van Kleef ◽  
Jacob M. Milikan ◽  
Marga Oortgiesen ◽  
Henk P.M. Vijverberg
Keyword(s):  
Nicotinic Acetylcholine Receptors ◽  
Acetylcholine Receptors ◽  
Neuronal Nicotinic Acetylcholine Receptors ◽  
Nicotinic Acetylcholine

scholarly journals NMR Structure and Action on Nicotinic Acetylcholine Receptors of Water-soluble Domain of Human LYNX1

2011 ◽  
Vol 286 (12) ◽  
pp. 10618-10627 ◽  
Author(s):  
Ekaterina N. Lyukmanova ◽  
Zakhar O. Shenkarev ◽  
Mikhail A. Shulepko ◽  
Konstantin S. Mineev ◽  
Dieter D'Hoedt ◽  
...  
Keyword(s):  
Nicotinic Acetylcholine Receptors ◽  
Acetylcholine Receptors ◽  
Nmr Structure ◽  
Water Soluble ◽  
Gpi Anchor ◽  
Nicotinic Acetylcholine ◽  
Brain Functions ◽  
The Central Nervous System ◽  
High Concentrations

Discovery of proteins expressed in the central nervous system sharing the three-finger structure with snake α-neurotoxins provoked much interest to their role in brain functions. Prototoxin LYNX1, having homology both to Ly6 proteins and three-finger neurotoxins, is the first identified member of this family membrane-tethered by a GPI anchor, which considerably complicates in vitro studies. We report for the first time the NMR spatial structure for the water-soluble domain of human LYNX1 lacking a GPI anchor (ws-LYNX1) and its concentration-dependent activity on nicotinic acetylcholine receptors (nAChRs). At 5–30 μm, ws-LYNX1 competed with 125I-α-bungarotoxin for binding to the acetylcholine-binding proteins (AChBPs) and to Torpedo nAChR. Exposure of Xenopus oocytes expressing α7 nAChRs to 1 μm ws-LYNX1 enhanced the response to acetylcholine, but no effect was detected on α4β2 and α3β2 nAChRs. Increasing ws-LYNX1 concentration to 10 μm caused a modest inhibition of these three nAChR subtypes. A common feature for ws-LYNX1 and LYNX1 is a decrease of nAChR sensitivity to high concentrations of acetylcholine. NMR and functional analysis both demonstrate that ws-LYNX1 is an appropriate model to shed light on the mechanism of LYNX1 action. Computer modeling, based on ws-LYNX1 NMR structure and AChBP x-ray structure, revealed a possible mode of ws-LYNX1 binding.

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