| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
J. Biol. Chem., Vol. 269, Issue 15, 10983-10986, 04, 1994
VK Gribkoff, G Champigny, P Barbry, SI Dworetzky, NA Meanwell and M Lazdunski
Cystic fibrosis is a major inherited disorder involving abnormalities of
fluid and electrolyte transport in a number of different organs. Epithelial
cells of cystic fibrosis patients have a decreased capacity to secrete
chloride in response to cAMP-mobilizing agents because of the mutation of a
single gene. The gene product, the cystic fibrosis transmembrane
conductance regulator or CFTR, is a chloride channel. The most frequent
mutation is a deletion of phenylalanine in position 508 (delta F508-CFTR)
that reduces both the expression of the CFTR protein at the cell surface,
and the activity of the Cl- channel. This work presents the properties of
NS004, a substituted benzimidazolone, which is the first activator of
normal and mutant CFTR-associated chloride channels to be described. NS004
activated CFTR and delta F508-CFTR Cl- channels expressed in Xenopus
oocytes, and increased 125I efflux (via the Cl- channel) from Vero cells
expressing CFTR and delta F508-CFTR. Application of NS004 to the external
side of outside-out patches excised from these CFTR- and delta
F508-CFTR-expressing cells induced a marked and reversible increase in
channel activity.
The substituted benzimidazolone NS004 is an opener of the cystic fibrosis chloride channel
Department of Central Nervous System Biophysics and Molecular Biology, Bristol-Myers Squibb Pharmaceutical Research Institute, Wallingford, Connecticut 06492.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  S. Noel, C. Faveau, C. Norez, C. Rogier, Y. Mettey, and F. Becq Discovery of Pyrrolo[2,3-b]pyrazines Derivatives as Submicromolar Affinity Activators of Wild Type, G551D, and F508del Cystic Fibrosis Transmembrane Conductance Regulator Chloride Channels J. Pharmacol. Exp. Ther., October 1, 2006; 319(1): 349 - 359. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. L. Hamilton and M. Kiessling DCEBIO stimulates Cl- secretion in the mouse jejunum Am J Physiol Cell Physiol, January 1, 2006; 290(1): C152 - C164. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. L. Berger, C. O. Randak, L. S. Ostedgaard, P. H. Karp, D. W. Vermeer, and M. J. Welsh Curcumin Stimulates Cystic Fibrosis Transmembrane Conductance Regulator Cl- Channel Activity J. Biol. Chem., February 18, 2005; 280(7): 5221 - 5226. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Caci, C. Folli, O. Zegarra-Moran, T. Ma, M. F. Springsteel, R. E. Sammelson, M. H. Nantz, M. J. Kurth, A. S. Verkman, and L. J. V. Galietta CFTR activation in human bronchial epithelial cells by novel benzoflavone and benzimidazolone compounds Am J Physiol Lung Cell Mol Physiol, July 1, 2003; 285(1): L180 - L188. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. L. Dormer, R. Derand, C. M. McNeilly, Y. Mettey, L. Bulteau-Pignoux, T. Metaye, J.-M. Vierfond, M. A. Gray, L. J. V. Galietta, M. R. Morris, et al. Correction of delF508-CFTR activity with benzo(c)quinolizinium compounds through facilitation of its processing in cystic fibrosis airway cells J. Cell Sci., March 13, 2002; 114(22): 4073 - 4081. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Fischer, N. Fukuda, P. Barbry, B. Illek, C. Sartori, and M. A. Matthay Partial restoration of defective chloride conductance in {Delta}F508 CF mice by trimethylamine oxide Am J Physiol Lung Cell Mol Physiol, July 1, 2001; 281(1): L52 - L57. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Al-Nakkash, S. Hu, M. Li, and T.-C. Hwang A Common Mechanism for Cystic Fibrosis Transmembrane Conductance Regulator Protein Activation by Genistein and Benzimidazolone Analogs J. Pharmacol. Exp. Ther., April 13, 2001; 296(2): 464 - 472. [Abstract] [Full Text]
|
|
|
|
|
|
S. Singh, C. A. Syme, A. K. Singh, D. C. Devor, and R. J. Bridges Benzimidazolone Activators of Chloride Secretion: Potential Therapeutics for Cystic Fibrosis and Chronic Obstructive Pulmonary Disease J. Pharmacol. Exp. Ther., April 13, 2001; 296(2): 600 - 611. [Abstract] [Full Text]
|
|
|
|
|
|
C. M. Liedtke, D. Cody, and T. S. Cole Differential regulation of Cl{-} transport proteins by PKC in Calu-3 cells Am J Physiol Lung Cell Mol Physiol, April 1, 2001; 280(4): L739 - L747. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Bulteau, R. Derand, Y. Mettey, T. Metaye, M. R. Morris, C. M. McNeilly, C. Folli, L. J. V. Galietta, O. Zegarra-Moran, M. M. C. Pereira, et al. Properties of CFTR activated by the xanthine derivative X-33 in human airway Calu-3 cells Am J Physiol Cell Physiol, December 1, 2000; 279(6): C1925 - C1937. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. C. Devor, R. J. Bridges, and J. M. Pilewski Pharmacological modulation of ion transport across wild-type and Delta F508 CFTR-expressing human bronchial epithelia Am J Physiol Cell Physiol, August 1, 2000; 279(2): C461 - C479. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. A. Syme, A. C. Gerlach, A. K. Singh, and D. C. Devor Pharmacological activation of cloned intermediate- and small-conductance Ca2+-activated K+ channels Am J Physiol Cell Physiol, March 1, 2000; 278(3): C570 - C581. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. K. Singh, D. C. Devor, A. C. Gerlach, M. Gondor, J. M. Pilewski, and R. J. Bridges Stimulation of Cl- Secretion by Chlorzoxazone J. Pharmacol. Exp. Ther., February 1, 2000; 292(2): 778 - 787. [Abstract] [Full Text]
|
|
|
|
|
|
F. Becq, Y. Mettey, M. A. Gray, L. J. V. Galietta, R. L. Dormer, M. Merten, T. Metaye, V. Chappe, C. Marvingt-Mounir, O. Zegarra-Moran, et al. Development of Substituted Benzo[c]quinolizinium Compounds as Novel Activators of the Cystic Fibrosis Chloride Channel J. Biol. Chem., September 24, 1999; 274(39): 27415 - 27425. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. D. SCHULTZ, A. K. SINGH, D. C. DEVOR, and R. J. BRIDGES Pharmacology of CFTR Chloride Channel Activity Physiol Rev, January 1, 1999; 79(1): 109 - 144. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Illek, H. Fischer, and T. E. Machen II. Regulation of CFTR by small molecules including HCO-3 Am J Physiol Gastrointest Liver Physiol, December 1, 1998; 275(6): G1221 - G1226. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. He, S. Raman, Y. Guo, and W. W. Reenstra Cystic fibrosis transmembrane conductance regulator activation by cAMP-independent mechanisms Am J Physiol Cell Physiol, October 1, 1998; 275(4): C958 - C966. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. J. Kelley, C. U. Cotton, and M. L. Drumm Regulation of amiloride-sensitive sodium absorption in murine airway epithelium by C-type natriuretic peptide Am J Physiol Lung Cell Mol Physiol, June 1, 1998; 274(6): L990 - L996. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. J. Ackerman and D. E. Clapham Ion Channels -- Basic Science and Clinical Disease N. Engl. J. Med., May 29, 1997; 336(22): 1575 - 1586. [Full Text] [PDF]
|
|
|
|
|
|
D. N. Sheppard, S. M. Travis, H. Ishihara, and M. J. Welsh Contribution of Proline Residues in the Membrane-spanning Domains of Cystic Fibrosis Transmembrane Conductance Regulator to Chloride Channel Function J. Biol. Chem., June 21, 1996; 271(25): 14995 - 15001. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. J. V. Galietta, M. F. Springsteel, M. Eda, E. J. Niedzinski, K. By, M. J. Haddadin, M. J. Kurth, M. H. Nantz, and A. S. Verkman Novel CFTR Chloride Channel Activators Identified by Screening of Combinatorial Libraries Based on Flavone and Benzoquinolizinium Lead Compounds J. Biol. Chem., June 1, 2001; 276(23): 19723 - 19728. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| All ASBMB Journals | Molecular and Cellular Proteomics |
| Journal of Lipid Research | ASBMB Today |
