Get 20M+ Full-Text Papers For Less Than $1.50/day. Start a 14-Day Trial for You or Your Team.

Learn More →

Characterization of a 7,8-Benzoflavone Double Effect on CFTR Cl- Channel Activity

Characterization of a 7,8-Benzoflavone Double Effect on CFTR Cl- Channel Activity The human cystic fibrosis transmembrane conductance regulator (CFTR) is a member of the superfamily of adenosine triphosphate (ATP)-binding cassette (ABC) transporter ATPases. This protein forms a Cl- channel with a complex regulation; gene mutations cause cystic fibrosis disease. We investigated the interaction between the protein and the flavone UCCF-029 using the patch-clamp technique in the excised inside-out configuration in order to study the molecular mechanism of action for this potentiator on completely phosphorylated channel (25 U/ml protein kinase A) and a relatively low level of ATP (0.3 mm). Low concentrations of UCCF-029 (<50 nm) increase the open probability (p o), favoring the channel transition to an activated state, while high UCCF-029 (>50 nm) levels determine inhibition of the CFTR by a reduction of the total open time. Our data suggest that this drug can potentiate CFTR by binding to a specific site on the nucleotide binding domain, promoting dimer formation. The response of CFTR to variable concentrations of ATP is not modified by application of the potentiator UCCF-029 at either low, activatory, concentration or high, inhibitory, levels. Hence, we conclude that the potentiator may not interfere with binding of ATP but probably acts at an independent site in the protein, interacting directly with CFTR to modulate channel activity. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png The Journal of Membrane Biology Springer Journals

Characterization of a 7,8-Benzoflavone Double Effect on CFTR Cl- Channel Activity

Loading next page...
1
 
/lp/springer_journal/characterization-of-a-7-8-benzoflavone-double-effect-on-cftr-cl-uvs8BL3TQK

References (36)

Publisher
Springer Journals
Copyright
Copyright © 2007 by Springer Science+Business Media, LLC
Subject
Life Sciences; Human Physiology ; Biochemistry, general
ISSN
0022-2631
eISSN
1432-1424
DOI
10.1007/s00232-007-9066-4
pmid
17876495
Publisher site
See Article on Publisher Site

Abstract

The human cystic fibrosis transmembrane conductance regulator (CFTR) is a member of the superfamily of adenosine triphosphate (ATP)-binding cassette (ABC) transporter ATPases. This protein forms a Cl- channel with a complex regulation; gene mutations cause cystic fibrosis disease. We investigated the interaction between the protein and the flavone UCCF-029 using the patch-clamp technique in the excised inside-out configuration in order to study the molecular mechanism of action for this potentiator on completely phosphorylated channel (25 U/ml protein kinase A) and a relatively low level of ATP (0.3 mm). Low concentrations of UCCF-029 (<50 nm) increase the open probability (p o), favoring the channel transition to an activated state, while high UCCF-029 (>50 nm) levels determine inhibition of the CFTR by a reduction of the total open time. Our data suggest that this drug can potentiate CFTR by binding to a specific site on the nucleotide binding domain, promoting dimer formation. The response of CFTR to variable concentrations of ATP is not modified by application of the potentiator UCCF-029 at either low, activatory, concentration or high, inhibitory, levels. Hence, we conclude that the potentiator may not interfere with binding of ATP but probably acts at an independent site in the protein, interacting directly with CFTR to modulate channel activity.

Journal

The Journal of Membrane BiologySpringer Journals

Published: Sep 18, 2007

There are no references for this article.