The substituted benzimidazolone NS004 is an opener of the cystic fibrosis chloride channel
نویسندگان
چکیده
منابع مشابه
Benzimidazolone activators of chloride secretion: potential therapeutics for cystic fibrosis and chronic obstructive pulmonary disease.
The diseases of cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD) are characterized by mucus-congested airways. Agents that stimulate the secretion of Cl- are anticipated to facilitate mucociliary clearance and thus be of benefit in the treatment of CF and COPD. Recently 1-EBIO (1-ethyl-2-benzimidazolinone or 1-ethyl-1,3-dihydro-2H-benzimidazol-2-one) was shown to stimulate ...
متن کاملChloride channel and chloride conductance regulator domains of CFTR, the cystic fibrosis transmembrane conductance regulator.
CFTR is a cyclic AMP (cAMP)-activated chloride (Cl-) channel and a regulator of outwardly rectifying Cl- channels (ORCCs) in airway epithelia. CFTR regulates ORCCs by facilitating the release of ATP out of cells. Once released from cells, ATP stimulates ORCCs by means of a purinergic receptor. To define the domains of CFTR important for Cl- channel function and/or ORCC regulator function, mutan...
متن کاملIdentification of an ion channel-forming motif in the primary structure of CFTR, the cystic fibrosis chloride channel.
Synthetic peptides with sequences representing putative transmembrane (M) segments of CFTR (the cystic fibrosis transmembrane conductance regulator) were used as tools to identify the involvement of such segments in forming the ionic pore of the CFTR Cl- channel. Peptides with sequences corresponding to M2 and M6 form anion-selective channels after reconstitution in lipid bilayers. In contrast,...
متن کاملCystic fibrosis: The ‘bicarbonate before chloride’ hypothesis
The specific effects of some mutations that cause cystic fibrosis suggest that reduced HCO(3)(-) transport is the key to understanding cystic fibrosis pathology. But there is a puzzling discrepancy between measures of CFTR-mediated chloride conductance in expression systems and the sweat chloride values of patients.
متن کاملLocating the Anion-selectivity Filter of the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Chloride Channel
The cystic fibrosis transmembrane conductance regulator forms an anion-selective channel; the site and mechanism of charge selectivity is unknown. We previously reported that cysteines substituted, one at a time, for Ile331, Leu333, Arg334, Lys335, Phe337, Ser341, Ile344, Arg347, Thr351, Arg352, and Gln353, in and flanking the sixth membrane-spanning segment (M6), reacted with charged, sulfhydr...
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ژورنال
عنوان ژورنال: Journal of Biological Chemistry
سال: 1994
ISSN: 0021-9258
DOI: 10.1016/s0021-9258(19)78079-x