Document Detail


Positive allosteric modulation of α4β2 nAChR agonist induced behaviour.
MedLine Citation:
PMID:  22552114     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Neuronal cholinergic transmission is a prerequisite for proper CNS function. Consequently, disturbance of this system is associated with a number of pathophysiological conditions such as Parkinson's disease, Alzheimer's disease, schizophrenia and ADHD. Consequently, drug discovery efforts have spurred considerable research endeavours into identifying specific compounds for this system. Nicotinic acetylcholine receptors (nAChR) are ligand gated ion channels involved in cholinergic transmission. nAChRs are homo- or heteromeric pentamers with α4β2 receptors being the most abundant heteromer. The stoichiometry of α4β2 receptors can be either (α4)(3)(β2)(2) or (α4)(2)(β2)(3) representing channels with low (LS) or high (HS) sensitivity, respectively, to endogenous ligands. In the present study we applied the partial nAChR α4β2 LS and HS agonist NS3956 and the LS selective positive allosteric modulator NS9283 to investigate the role of α4β2 in Parkinson and pain models. In 6-OHDA lesioned rats, NS3956 increased rotational behaviour when rats were co-treated with nomifensine. This effect was absent in the presence of mecamylamine. In contrast, co-treatment with NS3956 and NS9283 reduced rotational behaviour in the animals. In a rat formalin pain model NS3956 induced an analgesic response that was strongly potentiated by NS9283. Finally in vitro experiments were applied to determine dopamine release from striatal minces. NS3956 induced a concentration dependent release while NS9283 was unable to potentiate agonist induced release. Together these results emphasize involvement of α4β2 nAChR in rotational and analgesic responses and confirm striatal α4β2 receptors to be of the HS form.
Authors:
F Rode; G Munro; D Holst; E Ø Nielsen; K B Troelsen; D B Timmermann; L C B Rønn; M Grunnet
Related Documents :
19355984 - Computational modeling of intramolecular and intermolecular communication in gpcrs.
11008064 - Molecular aspects of muscarinic receptor dimerization.
15721304 - Successful expression of a functional yeast g-protein-coupled receptor (ste2) in mammal...
22542954 - Involvement of microglial rhoa/rho-kinase pathway activation in the dopaminergic neuron...
18949084 - Carotid body at(4) receptor expression and its upregulation in chronic hypoxia.
22227334 - Igf-i receptor signaling pathway is involved in the neuroprotective effect of genistein...
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-4-4
Journal Detail:
Title:  Brain research     Volume:  -     ISSN:  1872-6240     ISO Abbreviation:  -     Publication Date:  2012 Apr 
Date Detail:
Created Date:  2012-5-3     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0045503     Medline TA:  Brain Res     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2012 Elsevier B.V. All rights reserved.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Comparative study on song behavior, and ultra-structural, electrophysiological and immunoreactive pr...
Next Document:  Resveratrol inhibits neointimal formation after arterial injury through an endothelial nitric oxide ...