The
cholinergic anti-inflammatory reflex (
CAIR) represents an important homeostatic regulatory mechanism for sensing and controlling the body's response to inflammatory stimuli. Vagovagal reflexes are an integral component of
CAIR whose anti-inflammatory effects are mediated by
acetylcholine (ACh) acting at α7
nicotinic acetylcholine receptors (α7nAChR) located on cells of the immune system. Recently, it is appreciated that
CAIR and α7nAChR also participate in the control of metabolic homeostasis. This has led to the understanding that defective vagovagal reflex circuitry underlying
CAIR might explain the coexistence of
obesity, diabetes, and
inflammation in the
metabolic syndrome. Thus, there is renewed interest in the α7nAChR that mediates
CAIR, particularly from the standpoint of
therapeutics. Of special note is the recent finding that α7nAChR agonist
GTS-21 acts at L-cells of the distal intestine to stimulate the release of two glucoregulatory and anorexigenic
hormones:
glucagon-like peptide-1 (GLP-1) and
peptide YY (PYY). Furthermore, α7nAChR agonist
PNU 282987 exerts trophic factor-like actions to support pancreatic β-cell survival under conditions of stress resembling diabetes. This review provides an overview of α7nAChR function as it pertains to
CAIR, vagovagal reflexes, and metabolic homeostasis. We also consider the possible usefulness of α7nAChR agonists for treatment of
obesity, diabetes, and
inflammation.