[(Dihydroindenyl)oxy]alkonic acid inhibits the cystic fibrosis transmembrane conductance regulator.
We investigated the effects of [(dihydroindenyl)oxy]alkaonic acid (DIOA) on the Cl(-) secretion in Calu-3 human airway epithelial cells that exclusively express the cystic fibrosis transmembrane conductance regulator (CFTR) as an apical Cl(-) channel. The 5'-nitro-2-(3-phenylpropylamino) benzoate (NPPB)-sensitive short-circuit current (I(sc)) and apical conductance were markedly reduced by DIOA (100 microM) in the presence and absence of isoproterenol (10 nM). Replacement of the butyl group in DIOA with a methyl group attenuated the inhibitory effects. The ED(50) of DIOA (17.0+/-1.0 microM) was almost equivalent to that of NPPB (15.6+/-2.1 microM). In conclusion, DIOA inhibits CFTR as strongly as NPPB does.
Ito
Y
Y
2nd Division (Respiratory Division), 2nd Department of Internal Medicine, School of Medicine, Nagoya University, Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan. itoyasu@med.nagoya-u.ac.jp
Aoyama
M
M
Yamada
N
N
Mizuno
Y
Y
Kume
H
H
Yamaki
K
K
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D002264:Carboxylic Acids / Q000494:pharmacology*; D002712:Chlorides / Q000378:metabolism; D005576:Colforsin / Q000494:pharmacology; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000037:antagonists & inhibitors* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D006016:Glycolates / Q000494:pharmacology; D006801:Humans; D007192:Indenes / Q000494:pharmacology*; D007545:Isoproterenol / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects; D009579:Nitrobenzoates / Q000494:pharmacology; D013997:Time Factors; D014407:Tumor Cells, Cultured
C059990:((dihydroindenyl)oxy)alkanoic acid; C505032:CFTR protein, human; D002264:Carboxylic Acids; D002712:Chlorides; D006016:Glycolates; D007192:Indenes; D009579:Nitrobenzoates; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D005576:Colforsin; D015124:8-Bromo Cyclic Adenosine Monophosphate; C058176:5-nitro-2-(3-phenylpropylamino)benzoic acid; C015765:MK 473; D007545:Isoproterenol