Objective: 

Chloride secretion by pulmonary epithelial cells involves the cystic fibrosis transmembrane conductance regulator Cl_- channel (CFTR). Since loss of function mutations of the cftr are associated with CF lung disease, pharmacological activation of CFTR could represent a therapeutic option in some cases, particular in class III - V mutations. The aim of the present study was to investigate the impact of the commonly used anesthetic 1-octanol on CFTR Cl^- channel activity.

Methods: 

Tissues dissected from freshly isolated Xenopus laevis lungs were used to perform transepithelial Ussing chamber measurements and the short-circuit current (I_SC) was recorded.

Results: 

Application of 1-octanol (1 mM) to the apical side resulted in an increase of the I_SC (11%, P<0.05) which is in accordance with an increased apical Cl^- secretion. For further characterization different Cl^- channel inhibitors were used. The 1-octanol induced stimulation of I_SC was inhibited by the common Cl^- channel inhibitor NPPB (5-Nitro-2-(3-phenylpropylamino) benzoic acid; 100 mM, apical side) but not affected by DIDS (4,4'-di-isothiocyanato-stilbene-2,2'-disulfonic acid; 500 mM, apical side). Further experiments were performed with glibenclamide (750 mM) and CFTR_Inh-172 (20 mM), since these two compounds are indicated to be more CFTR selective compared with NPPB. Both CFTR selective inhibitors abolished the 1-octanol induced effect.

Conclusion: 

The present study provides evidence that 1-octanol is able to activate the CFTR Cl^- channel in a native lung epithelium and thereby to stimulate Cl^- secretion. These data may represent a novel option of therapeutic strategies in CF patients with certain mutations in the cftr gene.