Tumor Necrosis Factor α Enhances Nicotinic Receptor Up-regulation via a p38MAPK-dependent Pathway
Gahring, Lorise C. | Osborne-Hereford, Amber V. | Vasquez-Opazo, Gustavo A. | Rogers, Scott W.
A response by key neuronal nicotinic acetylcholine receptors (nAChRs) to sustained nicotine exposure is up-regulation. Although this unusual receptor characteristic contributes to processes ranging from aging to addiction, the normal physiologic reason for this response is unknown. We find that up-regulation of [³H]epibatidine binding and function in HEK293 cells stably expressing α4β2-nAChR is significantly enhanced by co-application of the proinflammatory cytokine, tumor necrosis factor α. The mechanism of tumor necrosis factor α-enhanced up-regulation requires transcription, new protein synthesis, and signaling through p38MAPK as demonstrated by complete inhibition using SB 202190. This finding extends the possibilities for nAChR-inflammatory interactions in normal physiological processes and offers novel insights into endogenous mechanisms that can modify up-regulation.Show more [+] Less [-]