Conference paper

Publication year: 2007

Pages: 2263-2269

Journal: Life Sciences

Volume number: 80

Issue number: 24-25

ISSN: 0024-3205

eISSN: 1879-0631

DOI Link: https://doi.org/10.1016/j.lfs.2007.01.026

Conference: 2nd International Symposium on Non-Neuronal Acetylcholine

Publisher: Elsevier

Abstract: 
Acetylcholine (ACh), derived both from nerve fibres and from non-neuronal sources such as epithelial cells, is a major regulator of airway function. There is evidence that dysfunction of the neuronal cholinergic system is involved in the pathogenesis of asthma. Here, we asked whether the pulmonary non-neuronal ACh-synthesis and release machinery is altered in a rat and a mouse model of allergic airway disease. Animals were sensitized against ovalbumin, challenged by allergen inhalation, and sacrificed 24 or 48 h later. Targets of investigation were the high-affinity choline transporter-1 (CHT1), that mediates cellular uptake of choline, the ACh-synthesizing enzyme choline acetyltransferase (ChAT), the vesicular ACh transporter (VAChT), and the polyspecific organic cation transporters (OCT1-3), which are able to translocate choline and ACh across the plasma membrane. With cell-type specific distribution patterns, immunohistochemistry identified these proteins in airway epithelial cells and alveolar macrophages. Real-time RT-PCR revealed significant decreases in ChAT-, CHTI-, VAChT-, OCT-mRNA in the lung of sensitized and allergen challenged animals. These data were supported by immunohistochemistry, demonstrating reduced labeling intensity of airway epithelial cells. ChAT-, CHT1-, VAChT-, and OCT1-mRNA were also significantly reduced in cells recovered by bronchoalveolar lavage from sensitized and challenged rats. In conclusion, the pulmonary non-neuronal cholinergic system is down-regulated in acute allergic airway inflammation. In view of the role of ACh in maintenance of cell-cell-contacts, stimulation of fluid-secretion and of ciliary beat frequency, this down-regulation may contribute to epithelial shedding and ciliated cell dysfunction that occur in this pathological condition. (c) 2007 Elsevier Inc. All rights reserved.

Harvard Citation style: Lips, K., Luehrmann, A., Tschernig, T., Stoeger, T., Alessandrini, F., Grau, V., et al. (2007) Down-regulation of the non-neuronal acetylcholine synthesis and release machinery in acute allergic airway inflammation of rat and mouse, Life Sciences, 80(24-25), pp. 2263-2269. https://doi.org/10.1016/j.lfs.2007.01.026

APA Citation style: Lips, K., Luehrmann, A., Tschernig, T., Stoeger, T., Alessandrini, F., Grau, V., Haberberger, R., Koepsell, H., Pabst, R., & Kummer, W. (2007). Down-regulation of the non-neuronal acetylcholine synthesis and release machinery in acute allergic airway inflammation of rat and mouse. Life Sciences. 80(24-25), 2263-2269. https://doi.org/10.1016/j.lfs.2007.01.026