Acetylcholine beyond neurons: the non‐neuronal cholinergic system in humans

Abstract

Animal life is controlled by neurons and in this setting cholinergic neurons play an important role. Cholinergic neurons release ACh, which via nicotinic and muscarinic receptors (n-and mAChRs) mediate chemical neurotransmission, a highly integrative process. Thus, the organism responds to external and internal stimuli to maintain and optimize survival and mood. Blockade of cholinergic neurotransmission is followed by immediate death. However, cholinergic communication has been established from the beginning of life in primitive organisms such as bacteria, algae, protozoa, sponge and primitive plants and fungi, irrespective of neurons. Tubocurarine-and atropine-sensitive effects are observed in plants indicating functional significance. All components of the cholinergic system (ChAT, ACh, n-and mAChRs, high-affinity choline uptake, esterase) have been demonstrated in mammalian non-neuronal cells, including those of humans. Embryonic stem cells (mice), epithelial, endothelial and immune cells synthesize ACh, which via differently expressed patterns of n-and mAChRs modulates cell activities to respond to internal or external stimuli. This helps to maintain and optimize cell function, such as proliferation, differentiation, formation of a physical barrier, migration, and ion and water movements. Blockade of n-and mACHRs on noninnervated cells causes cellular dysfunction and/or cell death. Thus, cholinergic signalling in non-neuronal cells is comparable to cholinergic neurotransmission. Dysfunction of the non-neuronal cholinergic system is involved in the pathogenesis of diseases. Alterations have been detected in inflammatory processes and a pathobiologic role of non-neuronal ACh in different diseases is discussed. The present article reviews recent findings about the non-neuronal cholinergic system in humans.

Plasticity of the murine spleen T-cell cholinergic receptors and their role in in vitro differentiation of naïve CD4 T cells toward the Th1, Th2 and Th17 lineages

“…1,2 Its role in the development of T cells and generation of specific T-cell repertoire is being intensively studied. Human lymphocytes express cholinergic receptors and enzymes that constitute an independent non-neuronal cholinergic system, or ACh axis, that can either upregulate or downregulate the immune response.…”

ELIC-α7 Nicotinic Acetylcholine Receptor (α7nAChR) Chimeras Reveal a Prominent Role of the Extracellular-Transmembrane Domain Interface in Allosteric Modulation

“…The ␣7 nicotinic acetylcholine receptor (␣7nAChR) 2 is a homopentameric acetylcholine-gated cation channel mediating fast synaptic transmission in neuronal cells (1) and calcium signaling in nonneuronal cells (2). The diverse biological functions of ␣7nAChR have made it a promising therapeutic target for numerous medical conditions, including pain (3,4), inflammation (5), cardiovascular disease (6), and a variety of psychiatric and neurological disorders (7)(8)(9).…”

Contribution of α7 nicotinic receptor to airway epithelium dysfunction under nicotine exposure

“…ACh, in addition to exogenous nicotine, regulates airway epithelium function via paracrine and autocrine mechanisms through nicotinic acetylcholine receptors (nAChRs) (10). Recently, nAChRs have been shown to participate in the control of the airway ion transport processes in mice (11).…”

“…Recently, nAChRs have been shown to participate in the control of the airway ion transport processes in mice (11). CFTR as well as components of the nonneuronal cholinergic system (10,12), including α7 nAChR (13) and choline acetyltransferase (14), are present at the apical membrane of airway ciliated cells. The α7 nAChR is characterized by a high Ca 2+ permeability (15).…”