Bioelectric effects of quinine on polarized airway epithelial cells.
Quinine has been increasingly utilized as a placebo in cystic fibrosis (CF) clinical trials, including those leading to FDA approval of inhaled tobramycin, recent studies of anti-inflammatory aerosols such as glutathione, and clinical testing of hypertonic saline aerosols to augment mucous clearance. The drug effectively masks taste of experimental therapeutics, but could also confer changes in processes contributing to CF pathogenesis, including chloride secretion and paracellular ion permeability. In the Ussing chamber, concentrations of quinine (1 mg/ml) anticipated in the airways of CF subjects after aerosolization led to changes in chloride transport in Calu-3 (airway serous glandular) cell monolayers. Tissue resistance was significantly disrupted by the compound in both Calu-3 and primary airway epithelial cells in vitro. Lower doses of quinine (between 10 and 100 microg/ml) strongly inhibited the chloride secretory mechanism that utilizes CFTR, and forskolin activated I(SC) was reduced by approximately 24% and 44% in the presence of 10 and 100 microg/ml quinine, respectively. Our findings indicate that quinine disrupts airway epithelial functional integrity and blocks transepithelial chloride transport. The use of quinine as a taste-masking agent may have bioelectric effects relevant to CF trials using aerosolized drug delivery.
Bates
Eleanor
E
Gregory Fleming James Cystic Fibrosis Research Center, University of Alabama at Birmingham, 1900 University Boulevard, Birmingham, AL 35294, USA.
Miller
Stacey
S
Alexander
Mariah
M
Mazur
Marina
M
Fortenberry
James A
JA
Bebok
Zsuzsa
Z
Sorscher
Eric J
EJ
Rowe
Steven M
SM
D002478:Cells, Cultured; D002712:Chlorides / Q000378:metabolism*; D003550:Cystic Fibrosis / Q000378:metabolism*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000502:physiology; D004847:Epithelial Cells / Q000187:drug effects*; D006801:Humans; D010539:Permeability / Q000187:drug effects; D010919:Placebos; D011803:Quinine / Q000494:pharmacology*; D012137:Respiratory System / Q000187:drug effects*
D002712:Chlorides; D010919:Placebos; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D011803:Quinine