Linked Life Data

17582383

Source:http://linkedlifedata.com/resource/pubmed/id/17582383

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
10
pubmed:dateCreated
2007-10-15
pubmed:abstractText
The sulfonylurea glibenclamide is widely used as an open-channel blocker of the CFTR chloride channel. Here, we used site-directed mutagenesis to identify glibenclamide site of interaction: a positively charged residue K978, located in the cytoplasmic loop 3. Charge-neutralizing mutations K978A, K978Q, K978S abolished the inhibition of forskolin-activated CFTR chloride current by glibenclamide but not by CFTR(inh)-172. The charge-conservative mutation K978R did not alter glibenclamide sensitivity of CFTR current. Mutations of the neighbouring R975 (R975A, R975S, R975Q) did not affect electrophysiological and pharmacological properties of CFTR. No alteration of halide selectivity was observed with any of these CFTR mutant channels. This study identifies a novel potential inhibitor site within the CFTR molecule, and suggests a novel role of cytoplasmic loop three, within the second transmembrane domain of CFTR protein. This work is the first to report on the role of a residue in a cytoplasmic loop in the mechanism of action of the channel blocker glibenclamide.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0006-3002
pubmed:author
pubmed:issnType
Print
pubmed:volume
1768
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2438-46
pubmed:meshHeading
pubmed:year
2007
pubmed:articleTitle
CFTR inhibition by glibenclamide requires a positive charge in cytoplasmic loop three.
pubmed:affiliation
Institut de Physiologie et Biologie Cellulaires, Université de Poitiers, CNRS UMR 6187, 86022 Poitiers cedex, France. patricia.melin@univ-poitiers.fr
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't