[Benzamil and mucoviscidosis. Primary culture of nasal mucosa as an electrophysiologic in vitro model].

The genetic disease cystic fibrosis (CF) is characterized by a defect in the gene encoding for an epithelial chloride channel. This gene product, cystic fibrosis transmembrane conductance regulator (CFTR), in turn leads to a decreased chloride secretion. When this occurs sodium absorption is increased drastically because of an up-regulation of the epithelial sodium channel. In airway epithelia these changes in ion permeabilities result in dehydration of the mucus blanket and impaired mucociliary clearance, and subsequently lead to chronic infections of the airways. In this study we established a primary cell culture of human nasal epithelium from CF and non-CF patients. The increased transepithelial potential in CF exclusively was due to the greater sodium absorption. In previous studies, amiloride was found to specifically block the epithelial sodium channel. Inhalation of nebulized amiloride has been used clinically in the treatment of CF to inhibit sodium absorption and exert a secondary effect on water withdrawal. In the present cell culture model benzamil, an amiloride analogue, was found to inhibit sodium absorption completely, but at strikingly lower concentrations than amiloride. This raises the possibility of using benzamil for inhalation and to provide better efficacy in the symptomatic therapy of patients with CF.