Activation of muscarinic receptor signaling by bile acids: physiological and medical implications

Abstract

Besides their known physiological actions, bile acids are signaling molecules that alter cell function by interacting with muscarinic and nuclear receptors. Bile acid interaction with nuclear receptors modulates bile acid and cholesterol metabolism, whereas the potential consequences of muscarinic receptor activation are much broader. This review examines recent discoveries regarding bile acid interaction with muscarinic receptors. Selective and functional bile acid interaction has been reported with M3 receptors expressed in guinea pig gastric chief cells, human colon cancer cells, and transfected Chinese hamster ovary cells. Interaction of bile acids with chief cells may contribute to mucosal damage and other pathophysiological consequences of bile reflux. Bile acid-induced stimulation of muscarinic receptors on colon cancer cells may contribute to cellular proliferation and neoplasia. Potential consequences of bile acid interaction with muscarinic receptors on gastrointestinal myocytes, biliary epithelium, vascular endothelium and dermal neurons are discussed. Elucidation of molecular mechanisms underlying interaction of bile acids with muscarinic receptors may suggest new treatments for conditions that result from such interactions.