Non-neuronal functions of acetylcholine via muscarinic receptor subtypes: cellular proliferation and differentiation in mammals

Abstract

Acetylcholine (ACh) is considered a neurotransmitter in central, parasympathetic, and neuromuscular synapses of mammals. Many of the important physiological functions of ACh are caused by the interaction of ACh with a group of G protein-coupled receptors (GPCRs) referred to as muscarinic ACh receptors (mAChRs). GPCRs are divided into five molecularly distinct muscarinic receptor subtypes that are referred to as M1-M5. M1-M5 receptors are abundantly expressed in most cells and tissues and are critically involved in cellular function, proliferation, and differentiation. Non-neuronal cells, including murine embryonic stem cells, epithelial cells, endothelial cells, and immune cells, synthesize ACh, which modulates cellular activities via ACh receptors (muscarinic and nicotinic receptors) in response to internal and external stimuli. Recently, we revealed that via activation of mAChRs, endogenously released ACh from intestinal epithelial cells contributes to the maintenance of somatic stem cells and the inhibition of differentiation to intestinal epithelial cells. Therefore, non-neuronal ACh production results in autocrine and paracrine promotion of cell proliferation and differentiation of embryonic and somatic stem cells.