Bronchorelaxation of the human bronchi by CFTR activators |
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| Affiliation: | 1. Institut de Physiologie et Biologie Cellulaires CNRS FRE3511, Université de Poitiers, Poitiers, France;2. Service de chirurgie cardiothoracique, CHU La Milétrie, Poitiers, France;1. Unidad de Biotecnología del Centro de Investigación Científica de Yucatán A.C., Calle 43, No. 130, Col. Chuburná de Hidalgo, CP 97200 Mérida, Yucatán, Mexico;2. División de Biología Celular y Molecular, Centro de Investigación Biomédica del Noreste, IMSS, San Luis Potosí y 2 de Abril, Col. Independencia, CP 65720 Monterrey, Nuevo León, Mexico;3. Departamento de Ciencias Básicas, División de Ciencia de la Salud, Universidad de Monterrey, Ave. Ignacio Morones Prieto 4500 Pte., CP 66238 San Pedro Garza García, Nuevo León, Mexico;4. Unidad de Recursos Naturales del Centro de Investigación Científica de Yucatán A.C., Calle 43, No. 130, Col. Chuburná de Hidalgo, CP 97200 Mérida, Yucatán, Mexico;1. Chest Research Foundation, Marigold, Kalyaninagar, Pune 411014, India;2. Department of Respiratory Medicine, BYL Nair Hospital, Mumbai, India;3. Cipla Ltd., Mumbai, India;1. Sir Peter Mansfield Magnetic Resonance Centre, School of Physics and Astronomy, The University of Nottingham, Nottingham, UK;2. Division of Therapeutics and Molecular Medicine, University of Nottingham, UK;3. Procter & Gamble, Whitehall Lane, Egham, Surrey, UK;4. Procter & Gamble, Mason, OH, USA |
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| Abstract: | The airway functions are profoundly affected in many diseases including asthma, COPD and cystic fibrosis (CF). CF the most common lethal autosomal recessive genetic disease is caused by mutations of the CFTR (Cystic Fibrosis transmembrane Conductance Regulator) gene, which normally encodes a multifunctional and integral membrane cAMP regulated and ATP gated Cl− channel expressed in airway epithelial cells.Using human lung tissues obtained from patients undergoing surgery for lung cancer, we demonstrated that CFTR participates in bronchorelaxation. Using human bronchial smooth muscle cells (HBSMC), we applied iodide influx assay to analyze the CFTR-dependent ionic transport and immunofluorescence technique to localize CFTR proteins. Moreover, the relaxation was studied in isolated human bronchial segments after pre-contraction with carbachol to determine the implication of CFTR in bronchodilation.We found in HBSMC that the pharmacology and regulation of CFTR is similar to that of its epithelial counterpart both for activation (using forskolin/genistein or a benzo[c]quinolizinium derivative) and for inhibition (CFTRinh-172 and GPinh5a). With human bronchial rings, we observed that whatever the compound used including salbutamol, the activation of muscular CFTR leads to a bronchodilation after constriction with carbachol.Altogether, these observations revealed that CFTR in the human airways is expressed in bronchial smooth muscle cells and can be pharmacologically manipulated leading to the hypothesis that this ionic channel could contribute to bronchodilation in human. |
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| Keywords: | Human airway Smooth muscle CFTR Relaxation Pharmacology |
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