Role of the α7 Nicotinic Acetylcholine Receptor and RIC-3 in the Cholinergic Anti-inflammatory Pathway

Cent Nerv Syst Agents Med Chem. 2017;17(2):90-99. doi: 10.2174/1871524916666160829114533.


Background: The nicotinic acetylcholine receptor (nAChR) gene family encodes for subunits of acetylcholine gated ion channels. These receptors are expressed widely and have many functions: They mediate excitation at neuro-muscular junctions. Nicotinic Acetylcholine Receptor: In the central nervous system nAChRs have been implicated in memory, cognition, and addiction. And in non-excitatory cells they regulate differentiation, proliferation and inflammatory responses. The CHRNA7 gene encodes for the α7 nAChR subunit that assembles into a homomeric receptor having unusual properties. It is expressed widely and has many functions atypical for nAChRs; specifically, in immune cells α7 is required for the anti-inflammatory effects of acetylcholine and has been implicated in inflammatory autoimmune diseases including Multiple Sclerosis (MS). Interestingly, although, α7 receptors are found at the outer membranes of immune cells, acetylcholine-dependent currents have not been recorded from these cells. Therefore, its mechanism of action in immune cells needs further evaluation. Maturation of α7 into functional ligand-gated channels in the plasma membrane is a complex process shown to depend on the ER-resident chaperone, RIC-3. Therefore, RIC-3 regulates functional expression of α7. RIC-3 like α7 is expressed in immune cells and has been implicated in MS. Thus, RIC-3 may regulate functional expression of α7 in immune cells.

Conclusion: In this review we describe effects and mechanism of action of α7 nAChR and RIC-3 in the immune cholinergic system. Elucidating these mechanisms and the regulation of α7 and RIC-3 in the immune cholinergic system can pave the way for novel immunomodulatory agents, or towards extending the application of cholinergic agents.

Keywords: Cholinergic anti-inflammatory pathway; RIC-3; acetylcholine esterase inhibitors; metabotropic cholinergic signaling; multiple sclerosis; α7 nicotinic acetylcholine receptor.

Publication types

  • Review

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Anti-Inflammatory Agents / therapeutic use*
  • Cholinergic Agents / pharmacology
  • Cholinergic Agents / therapeutic use*
  • Humans
  • Immunologic Factors / pharmacology
  • Immunologic Factors / therapeutic use
  • Inflammation / drug therapy
  • Inflammation / immunology
  • Inflammation Mediators / antagonists & inhibitors
  • Inflammation Mediators / immunology*
  • Intracellular Signaling Peptides and Proteins / physiology*
  • Signal Transduction / drug effects
  • Signal Transduction / physiology*
  • alpha7 Nicotinic Acetylcholine Receptor / physiology*


  • Anti-Inflammatory Agents
  • Cholinergic Agents
  • Immunologic Factors
  • Inflammation Mediators
  • Intracellular Signaling Peptides and Proteins
  • RIC3 protein, human
  • alpha7 Nicotinic Acetylcholine Receptor