Abstract
Nicotinic acetylcholine receptors (nAChR) are widely distributed in neuronal and non-neuronal tissues, where they play diverse physiological roles. In this review, we highlight the recent findings regarding the role of nAChR in the respiratory tract with a special focus on the involvement of nAChR in the regulation of multiple processes in health and disease. We discuss the role of nAChR in mucociliary clearance, inflammation, and infection and in airway diseases such as asthma, chronic obstructive pulmonary disease, and cancer. The subtype diversity of nAChR enables differential regulation, making them a suitable pharmaceutical target in many diseases. The stimulation of the α3β4 nAChR could be beneficial in diseases accompanied by impaired mucociliary clearance, and the anti-inflammatory effect due to an α7 nAChR stimulation could alleviate symptoms in diseases with chronic inflammation such as chronic obstructive pulmonary disease and asthma, while the inhibition of the α5 nAChR could potentially be applied in non-small cell lung cancer treatment. However, while clinical studies targeting nAChR in the airways are still lacking, we suggest that more detailed research into this topic and possible pharmaceutical applications could represent a valuable tool to alleviate the symptoms of diverse airway diseases.
Highlights
Nicotinic acetylcholine receptors are widely distributed in diverse neuronal and non-neuronal tissues
This assumption is based on the increased proliferative effect of nicotine and a Nicotinic acetylcholine receptors (nAChR)-dependent upregulation of ACE2, as ACE2 has previously been shown to play a role in COVID-19 infection [79]
These studies show that inhibiting α5 nAChR might represent a promising target for therapy for nicotine-induced non-small cell lung cancer
Summary
Nicotinic acetylcholine receptors (nAChR) are widely distributed in diverse neuronal and non-neuronal tissues They form various subtypes consisting of different subunit combinations. All of the aforementioned studies show that while some differences might exist between species in terms of the expression of the various nAChR subunits, they seem to be broadly expressed and to play an essential role for the functions of the respiratory tract. NAChR display a wide variety of effects and properties This is based on the multitude of subunits present in different cell types in the respiratory tract, which results in various possibilities for the assembly of these subunits. The nAChR subtypes display diverse physiological properties, as discussed in this review, since their function depends on the subunit composition and on their affinity to their endogenous ligand ACh
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