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A G protein‐coupled α7 nicotinic receptor regulates signaling and TNF‐α release in microglia

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dc.contributor.author King, Justin R.
dc.contributor.author Gillevet, Trudy C.
dc.contributor.author Kabbani, Nadine
dc.date.accessioned 2019-02-15T18:26:06Z
dc.date.available 2019-02-15T18:26:06Z
dc.date.issued 2017-07
dc.identifier.issn 2211-5463
dc.identifier.uri http://hdl.handle.net/1920/11387
dc.description.abstract Acetylcholine activation of α7 nicotinic acetylcholine receptors (α7 nAChRs) in microglia attenuates neuroinflammation and regulates TNF‐α release. We used lipopolysaccharide to model inflammation in the microglial cell line EOC20 and examined signaling by the α7 nAChR. Co‐immunoprecipitation experiments confirm that α7 nAChRs bind heterotrimeric G proteins in EOC20 cells. Interaction with Gαi mediates α7 nAChR signaling via enhanced intracellular calcium release and a decrease in cAMP, p38 phosphorylation, and TNF‐α release. These α7 nAChR effects were blocked by the inhibition of Gαi signaling via pertussis toxin, PLC activity with U73122, and α7 nAChR channel activity with the selective antagonist α‐bungarotoxin. Moreover, α7 nAChR signaling in EOC20 cells was significantly diminished by the expression of a dominant‐negative α7 nAChR, α7345‐8A, shown to be impaired in G protein binding. These findings indicate an essential role for G protein coupling in α7 nAChR function in microglia leading to the regulation of inflammation in the nervous system. en_US
dc.language.iso en_US en_US
dc.publisher FEBS Open Bio en_US
dc.rights Attribution 3.0 United States *
dc.rights.uri http://creativecommons.org/licenses/by/3.0/us/ *
dc.title A G protein‐coupled α7 nicotinic receptor regulates signaling and TNF‐α release in microglia en_US
dc.type Article en_US
dc.identifier.doi 10.1002/2211-5463.12270


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