Tumor Necrosis Factor α Enhances Nicotinic Receptor Up-regulation via a p38MAPK-dependent Pathway*
- Lorise C. Gahring‡§,1,
- Amber V. Osborne-Hereford¶,2,
- Gustavo A. Vasquez-Opazo§ and
- Scott W. Rogers‡∥
- ‡Salt Lake City Veterans Affairs-Geriatrics Research, Education, and Clinical Center, Salt Lake City, Utah 84148 and the Departments of §Internal Medicine, ¶Pathology, and ∥Neurobiology and Anatomy, University of Utah, Salt Lake City, Utah 84132
- ↵1 To whom correspondence should be addressed: University of Utah School of Medicine 2C132, 30 North 1900 East, Salt Lake City, UT 84132. Fax: 801-585-3884; E-mail: Lorise.Gahring{at}hsc.utah.edu.
Abstract
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.
- Received August 31, 2007.
- Revision received October 29, 2007.
- The American Society for Biochemistry and Molecular Biology, Inc.
