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

Acetylcholine activation of α7 nicotinic acetylcholine receptors (α7nAChRs) in microglia attenuates neuroinflammation and regulatesTNF‐α release. We used lipopolysaccharide to model inflammation in the microglial cell lineEOC20 and examined signaling by the α7nAChR. Co‐immunoprecipitation experiments confirm that α7nAChRs bind heterotrimeric G proteins inEOC20 cells. Interaction with Gαi mediates α7nAChRsignaling via enhanced intracellular calcium release and a decrease incAMP, p38 phosphorylation, andTNF‐α release. These α7nAChReffects were blocked by the inhibition of Gαi signaling via pertussis toxin,PLCactivity with U73122, and α7nAChRchannel activity with the selective antagonist α‐bungarotoxin. Moreover, α7nAChRsignaling inEOC20 cells was significantly diminished by the expression of a dominant‐negative α7nAChR, α7345‐8A,shown to be impaired in G protein binding. These findings indicate an essential role for G protein coupling in α7nAChRfunction in microglia leading to the regulation of inflammation in the nervous system.