Abstract
The cystic fibrosis transmembrane conductance regulator (CFTR) is associated with expression of a chloride conductance that is defective in cystic fibrosis (CF). Xenopus oocytes injected with RNA coding for CFTR that contained mutations in the first nucleotide binding fold (NBF1) expressed chloride currents in response to raising adenosine 3',5'-monophosphate (cAMP) with forskolin and 3-isobutyl-1-methylxanthine (IBMX). The mutant CFTRs were less sensitive than wild-type CFTR to this activating stimulus, and the reduction in sensitivity correlated with the severity of cystic fibrosis in patients carrying the corresponding mutations. This demonstration provides the basis for detailed analyses of NBF1 function and suggests potential pharmacologic treatments for cystic fibrosis.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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1-Methyl-3-isobutylxanthine / pharmacology
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Animals
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Chloride Channels
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Chlorides / metabolism*
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Cystic Fibrosis / genetics
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Cystic Fibrosis / physiopathology
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Cystic Fibrosis Transmembrane Conductance Regulator
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Genetic Variation
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Genotype
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Humans
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Ion Channels / physiology
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Membrane Potentials / drug effects
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Membrane Proteins / drug effects
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Membrane Proteins / genetics
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Membrane Proteins / physiology*
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Microinjections
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Mutation*
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Oocytes / drug effects
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Oocytes / physiology*
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RNA / administration & dosage
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RNA / genetics
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Transcription, Genetic
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Xenopus
Substances
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CFTR protein, human
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Chloride Channels
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Chlorides
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Ion Channels
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Membrane Proteins
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Cystic Fibrosis Transmembrane Conductance Regulator
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RNA
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1-Methyl-3-isobutylxanthine