LOCALIZATION OF α7 NICOTINIC ACETYLCHOLINE RECEPTOR mRNA AND PROTEIN WITHIN THE CHOLINERGIC ANTI-INFLAMMATORY PATHWAY

Electrical stimulation of the vagus nerve attenuates tumor necrosis factor (TNF) synthesis by macrophages and reduces the systemic inflammatory response. Current evidence suggests that the alpha 7 nicotinic acetylcholine receptor present in the celiac/superior mesenteric ganglia is a key component in vagus nerve signaling to the spleen; however, there is currently no direct anatomical evidence that the alpha 7 receptor is present in the murine celiac/superior mesenteric ganglia. Our study addresses this deficiency by providing anatomical evidence that the alpha 7 receptor is expressed within the celiac/superior mesenteric ganglia and splenic nerve fibers using immunohistochemistry and quantitative polymerase chain reaction (qPCR). alpha 7 receptor mRNA is highly expressed in the celiac/superior mesenteric ganglia and at low levels in the spleen compared to the brain. Double-labeling for alpha 7 and tyrosine hydroxylase shows that alpha 7 receptor protein is present on noradrenergic neurons within the ganglia and prejunctionally on noradrenergic nerve fibers within the spleen. The alpha 7 receptor in the ganglia provides a possible location for the action of alpha 7-selective agonists, while prejunctional alpha 7 receptor expressed on splenic nerves may induce an increase in norepinephrine release in a positive feedback system enhanced by lymphocyte-derived acetylcholine. (C) 2014 IBRO. Published by Elsevier Ltd. All rights reserved.