The role of alpha7 nicotinic acetylcholine receptors in inflammatory bowel disease: involvement of different cellular pathways

Expert Opin Ther Targets. 2018 Feb;22(2):161-176. doi: 10.1080/14728222.2018.1420166. Epub 2018 Jan 3.

Abstract

Autonomic imbalance plays a pivotal role in the pathophysiology of inflammatory bowel diseases (IBD). The central nervous system (CNS) cooperates dynamically with the immune system to regulate inflammation through humoral and neural pathways. In particular, acetylcholine (Ach), the main neurotransmitter in the vagus nerve, decreases the production of pro-inflammatory cytokines through a mechanism dependent on the α7 nicotinic Ach receptors (α7nAChRs). Areas covered: Here, we review the evidence for involvement of the cholinergic anti-inflammatory pathway (CAP) in IBD. We also elaborate the role of α7nAChRs and subsequent cellular pathways in CAP. Finally, we review potential therapeutic implications of modulators of these receptors. Expert opinion: Alpha7nAChR modulators possess both cognitive improving and anti-inflammatory properties. Although, these agents demonstrated therapeutic benefits in experimental models, their efficacy has not always been translated in clinical trials. Thus, development of more specific α7nAChR ligands as well as more experimental studies and better controlled trials, especially in the field of IBD, are encouraged for a progress in this field.

Keywords: cytokines; immune cells; inflammatory bowel disease; intracellular pathways; α7nAChR.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Acetylcholine / metabolism
  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • Cytokines / metabolism
  • Drug Design
  • Humans
  • Inflammation / drug therapy
  • Inflammation / physiopathology
  • Inflammatory Bowel Diseases / drug therapy
  • Inflammatory Bowel Diseases / physiopathology*
  • Ligands
  • alpha7 Nicotinic Acetylcholine Receptor / drug effects
  • alpha7 Nicotinic Acetylcholine Receptor / metabolism*

Substances

  • Anti-Inflammatory Agents
  • Cytokines
  • Ligands
  • alpha7 Nicotinic Acetylcholine Receptor
  • Acetylcholine

Grant support