Dysfunction of the non-neuronal cholinergic system in the airways and blood cells of patients with cystic fibrosis

Wessler, Ignaz; Bittinger, Fernando; Kamin, Wolfgang; Zepp, Fred; Meyer, Eckhard; Schad, Arno; Kirkpatrick, Charles James

doi:10.1016/j.lfs.2007.01.042

Cited by 32 publications

(26 citation statements)

References 32 publications

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“…Therefore, sAC activation by nAChR could additionally increase CFTR amount and activity in CFTR mutation classes IV-V, in which functional CFTR is present, but its activity or the amount of functional protein is reduced (O'Sullivan and Freedman, 2009). A direct link between cystic fibrosis and cholinergic signaling has been previously established (Wessler et al, 2007). In this study, a down-regulation of the non-neuronal cholinergic system of the lung has been observed in cystic fibrosis (Wessler et al, 2007).…”

Section: Discussionmentioning

confidence: 50%

“…A direct link between cystic fibrosis and cholinergic signaling has been previously established (Wessler et al, 2007). In this study, a down-regulation of the non-neuronal cholinergic system of the lung has been observed in cystic fibrosis (Wessler et al, 2007). Therefore it could be hypothesized that patients with cystic fibrosis might show reduced nAChR mediated cholinergic signaling, which would contribute to the pathogenesis of the disease.…”

Section: Discussionmentioning

confidence: 50%

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Nicotine-induced activation of soluble adenylyl cyclase participates in ion transport regulation in mouse tracheal epithelium

et al. 2012

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Section: Discussionmentioning

confidence: 50%

Section: Discussionmentioning

confidence: 50%

Nicotine-induced activation of soluble adenylyl cyclase participates in ion transport regulation in mouse tracheal epithelium

et al. 2012

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“…Impairment of airway mucus transport results from dysfunction of CFTR. The nonneuronal cholinergic system also control mucus transport (33) and is deregulated in the airways of patients with CF (34). Recently, Hollenhorst et al observed that acute nicotine exposure modulated ion transport processes in the murine tracheal epithelium and this effect was mediated by nAChRs (11).…”

Section: Discussionmentioning

confidence: 99%

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

Maouche

Medjber

Zahm

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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Loss or dysfunction of the cystic fibrosis (CF) transmembrane conductance regulator (CFTR) leads to impairment of airway mucus transport and to chronic lung diseases resulting in progressive respiratory failure. Nicotinic acetylcholine receptors (nAChRs) bind nicotine and nicotine-derived nitrosamines and thus mediate many of the tobacco-related deleterious effects in the lung. Here we identify α7 nAChR as a key regulator of CFTR in the airways. The airway epithelium in α7 knockout mice is characterized by a higher transepithelial potential difference, an increase of amiloride-sensitive apical Na + absorption, a defective cAMP-dependent Cl − conductance, higher concentrations of Na + , Cl − , K + , and Ca 2+ in secretions, and a decreased mucus transport, all relevant to a deficient CFTR activity. Moreover, prolonged nicotine exposure mimics the absence of α7 nAChR in mice or its inactivation in vitro in human airway epithelial cell cultures. The functional coupling of α7 nAChR to CFTR occurs through Ca 2+ entry and activation of adenylyl cyclases, protein kinase A, and PKC. α7 nAChR, CFTR, and adenylyl cyclase-1 are physically and functionally associated in a macromolecular complex within lipid rafts at the apical membrane of surface and glandular airway epithelium. This study establishes the potential role of α7 nAChR in the regulation of CFTR function and in the pathogenesis of smoking-related chronic lung diseases.chloride efflux | ciliated cell | mouse | mucociliary clearance | submucosal gland

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“…ACh represents an important regulator of epithelial ion and water movements. In patients suffering from cystic fibrosis, the ACh content was markedly reduced [61]. Interestingly, mAChR and α 7 -nAChR seem to be regulators of CFTR [62,63].…”

Section: Respiratory Systemmentioning

confidence: 99%

The Non-Neuronal Cholinergic System in Health and Disease

Beckmann¹,

Lips²

2013

Pharmacology

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Acetylcholine (ACh) is not only a neurotransmitter but is an ancient molecule that can be released by and act on non-neuronal cells. In these cells the system of ACh-synthesizing enzymes, transporters, receptors and degrading enzymes is termed the non-neuronal cholinergic system (NNCS). There is increasing evidence that the NNCS is dysregulated in various diseases and can have an influence on their pathology. However, for many organ systems not much is known about the expression and function of the NNCS. Thus, this review focusses on the role of the NNCS in different organ systems in health and disease. Dysregulation of ACh synthesis and release, mutations or polymorphisms in genes encoding NNCS components, and auto-antibodies against NNCS components are common factors influencing disease progression. Pharmacological agents targeting the NNCS are already successfully in clinical use for some disorders, indicating that interfering with this system is very promising and more research is needed to elucidate the role of the NNCS in different tissues and pathological states.

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Dysfunction of the non-neuronal cholinergic system in the airways and blood cells of patients with cystic fibrosis

Cited by 32 publications

References 32 publications

Nicotine-induced activation of soluble adenylyl cyclase participates in ion transport regulation in mouse tracheal epithelium

Nicotine-induced activation of soluble adenylyl cyclase participates in ion transport regulation in mouse tracheal epithelium

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

The Non-Neuronal Cholinergic System in Health and Disease

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