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Evidence that CFTR is expressed in rat tracheal smooth muscle cells and contributes to bronchodilation.

Abstract : BACKGROUND: The airway functions are profoundly affected in many diseases including asthma, chronic obstructive pulmonary disease (COPD) and cystic fibrosis (CF). CF the most common lethal autosomal recessive genetic disease is caused by mutations of the CFTR gene, which normally encodes a multifunctional and integral membrane protein, the CF transmembrane conductance regulator (CFTR) expressed in airway epithelial cells. METHODS: To demonstrate that CFTR is also expressed in tracheal smooth muscle cells (TSMC), we used iodide efflux assay to analyse the chloride transports in organ culture of rat TSMC, immunofluorescence study to localize CFTR proteins and isometric contraction measurement on isolated tracheal rings to observe the implication of CFTR in the bronchodilation. RESULTS: We characterized three different pathways stimulated by the cAMP agonist forskolin and the isoflavone agent genistein, by the calcium ionophore A23187 and by hypo-osmotic challenge. The pharmacology of the cAMP-dependent iodide efflux was investigated in detail. We demonstrated in rat TSMC that it is remarkably similar to that of the epithelial CFTR, both for activation (using three benzo [c]quinolizinium derivatives) and for inhibition (glibenclamide, DPC and CFTRinh-172). Using rat tracheal rings, we observed that the activation of CFTR by benzoquinolizinium derivatives in TSMC leads to CFTRinh-172-sensitive bronchodilation after constriction with carbachol. An immunolocalisation study confirmed expression of CFTR in tracheal myocytes. CONCLUSION: Altogether, these observations revealed that CFTR in the airways of rat is expressed not only in the epithelial cells but also in tracheal smooth muscle cells leading to the hypothesis that this ionic channel could contribute to bronchodilation.
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Submitted on : Friday, September 22, 2006 - 3:45:13 PM
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Clarisse Vandebrouck, Patricia Melin, Caroline Norez, Renaud Robert, Christelle Guibert, et al.. Evidence that CFTR is expressed in rat tracheal smooth muscle cells and contributes to bronchodilation.. Respiratory Research, BioMed Central, 2006, 7, pp.113. ⟨10.1186/1465-9921-7-113⟩. ⟨inserm-00097884⟩



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