TY - JOUR
T1 - The α7 nicotinic acetylcholine receptor ligands methyllycaconitine, NS6740 and GTS-21 reduce lipopolysaccharide-induced TNF-α release from microglia
AU - Thomsen, Morten Skøtt
AU - Mikkelsen, Jens D
N1 - Copyright © 2012 Elsevier B.V. All rights reserved.
PY - 2012/10/15
Y1 - 2012/10/15
N2 - The anti-inflammatory properties of, particularly the α7, nicotinic acetylcholine receptors (nAChRs) in the peripheral immune system are well documented. There are also reports of anti-inflammatory actions of nicotine in the CNS, but it is unclear, whether this is due to activation or inhibition of nAChRs. Here we investigate the mechanisms behind α7 nAChR-mediated modulation of TNF-α release. We show that α7 nAChR agonists or positive allosteric modulators do not affect LPS-induced release of the pro-inflammatory cytokine TNF-α from cultured microglia. This suggests that classical activation of, i.e. ion-flux through, the α7 nAChR does not reduce TNF-α release from activated microglia. Contrarily, the α7 nAChR antagonist methyllycaconitine and the weak (
AB - The anti-inflammatory properties of, particularly the α7, nicotinic acetylcholine receptors (nAChRs) in the peripheral immune system are well documented. There are also reports of anti-inflammatory actions of nicotine in the CNS, but it is unclear, whether this is due to activation or inhibition of nAChRs. Here we investigate the mechanisms behind α7 nAChR-mediated modulation of TNF-α release. We show that α7 nAChR agonists or positive allosteric modulators do not affect LPS-induced release of the pro-inflammatory cytokine TNF-α from cultured microglia. This suggests that classical activation of, i.e. ion-flux through, the α7 nAChR does not reduce TNF-α release from activated microglia. Contrarily, the α7 nAChR antagonist methyllycaconitine and the weak (
KW - Aconitine
KW - Animals
KW - Anti-Inflammatory Agents
KW - Azabicyclo Compounds
KW - Benzylidene Compounds
KW - Furans
KW - Lipopolysaccharides
KW - MAP Kinase Signaling System
KW - Male
KW - Microglia
KW - Nicotinic Agonists
KW - Nicotinic Antagonists
KW - Pyridines
KW - Rats
KW - Rats, Sprague-Dawley
KW - Receptors, Nicotinic
KW - Tumor Necrosis Factor-alpha
KW - alpha7 Nicotinic Acetylcholine Receptor
U2 - 10.1016/j.jneuroim.2012.07.006
DO - 10.1016/j.jneuroim.2012.07.006
M3 - Journal article
C2 - 22884467
SN - 1872-8421
VL - 251
SP - 65
EP - 72
JO - Journal of Neuroimmunology
JF - Journal of Neuroimmunology
IS - 1-2
ER -