Cholinergic mechanisms of the airways: Medical education

Abstract

The human airways are innervated via efferent and afferent autonomic nerves, which regulate many aspects of airway function. Acetylcholine as the classical neurotransmitter of parasymphathetic nervous system regulates airway tone. In addition, the production of mucus in the central airways is also under cholinergic control. Cholinergic activity of the lung is more pronounced in large than in peripheral airways. Acetylcholine can act via two different classes of receptors, the nicotinic and muscarinic receptors. This neurotransmitter is also present in non-neural cells including leukocytes, smooth muscle cells, epithelial and endothelial cells. Besides, acetylcholine may in part regulate pathological changes associated with airway remodeling. M3 receptors are the predominant type mediating airway smooth muscle contraction but M2 receptors on the airway smooth muscle also activate RhoA-Rho kinase pathway. This pathway mediates a proliferative Stimulus and may cause inflammatory gene expression. There is a complex relation between inflammation and neural control of the airways. Vagal tone is increased in airway inflammation associated with asthma and chronic obstructive pulmonary disease. M2 receptor dysfunction on the airway neurons may be present in allergic airway inflammation by eosinophil-derived major basic protein. Similarly, an increased release of acetylcholine from parasymphathetic nerves seems to contribute to airway hyperresponsiveness associated with viral infection. This review summarizes the current knowledge of the cholinergic system in the airways.