8-cyclopentyl-1,3-dipropylxanthine and other xanthines differentially bind to the wild-type and delta F508 first nucleotide binding fold (NBF-1) domains of the cystic fibrosis transmembrane conductance regulator

Biochemistry
B E CohenH B Pollard

Abstract

Cystic fibrosis is an autosomal recessive disorder affecting chloride transport in pancreas, lung, and other tissues, which is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR). Certain alkyl xanthines such as CPX (8-cyclopentyl-1,3-dipropylxanthine) stimulate Cl- efflux from cells bearing the delta F508 genotype common to most cases of cystic fibrosis. We have hypothesized that the CFTR molecule itself might be the site for CPX action, perhaps in the region of the first nucleotide binding fold (NBF-1) domain. Therefore, to test this hypothesis directly we have used a rapid membrane filtration assay to measure the kinetics of association and dissociation of [3H]CPX to both recombinant NBF-1 and recombinant NBF-1 bearing the delta F508 mutation. We report that [3H]CPX binds with higher affinity to the delta F508-NBF-1 of CFTR (Kd = 1.0 nM) than to the wild-type NBF-1 of CFTR (Kd = 17.0 nM). These Kd values were calculated from direct measurements of the association and dissociation rate constants. The rate constants for the dissociation reaction of the wild-type NBF-1 and delta F508-NBF-1 of CFTR were not different from each other. However, the corresponding rate constants for the association ...Continue Reading

References

Jul 1, 1983·Analytical Biochemistry·R F BrunsT A Pugsley
Jan 1, 1996·Drug Development Research·A Michiel van Rhee, Kenneth A Jacobson

❮ Previous
Next ❯

Citations

Jan 22, 2002·Pediatric Pulmonology·Nael A McCartyRichard C Ahrens
May 9, 2000·Biochemical and Biophysical Research Communications·L D HowellJ A Cohn
Dec 7, 2007·Pflügers Archiv : European journal of physiology·Ivana NovakMette R Hansen
Mar 28, 2008·Purinergic Signalling·I Novak
Sep 25, 2002·Biochemical and Biophysical Research Communications·Charlotte AnderssonGodfried M Roomans
Nov 5, 1999·Trends in Pharmacological Sciences·T C Hwang, D N Sheppard
Nov 30, 2002·Advanced Drug Delivery Reviews·Kristina Powell, Pamela L Zeitlin
Oct 3, 2002·British Journal of Pharmacology·Olga Zegarra-MoranLuis J V Galietta
Nov 13, 2001·Clinical and Experimental Pharmacology & Physiology·K Kunzelmann, M Mall
Mar 18, 2000·Kidney International·P L Zeitlin
Feb 18, 1999·The Journal of Clinical Investigation·P L Zeitlin
May 5, 2010·AAPS PharmSciTech·Timothy McPhersonTonglei Li
Apr 23, 2002·Pharmacogenomics·Federica SangiuoloGiuseppe Novelli
Oct 8, 2004·Pharmacogenomics·Federica SangiuoloGiuseppe Novelli
Jun 27, 2002·American Journal of Pharmacogenomics : Genomics-related Research in Drug Development and Clinical Practice·O EidelmanH B Pollard
May 12, 2004·Proceedings of the National Academy of Sciences of the United States of America·Meera SrivastavaHarvey B Pollard
Dec 16, 2000·Expert Opinion on Investigational Drugs·G M Roomans
Dec 16, 2000·Expert Opinion on Investigational Drugs·D J Wallace
Dec 25, 2003·The Journal of Physiology·R Elaine Bucheimer, Joel Linden
May 29, 2007·Journal of Molecular Graphics & Modelling·Daniel J WarnerStephen W Doughty
Oct 6, 1998·Clinics in Chest Medicine·P L Zeitlin
Apr 18, 2003·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Marzena Karcz-KubichaSergi Ferré
Apr 15, 2014·Psychopharmacology·Sylvain DubroquaPhilipp Singer
Oct 15, 2003·The Journal of Pharmacology and Experimental Therapeutics·Zuzana JustinovaSteven R Goldberg
Jan 5, 2002·Physiological Reviews·Karl Kunzelmann, Marcus Mall
Oct 1, 1998·The American Journal of Physiology·Z HeW W Reenstra
Jan 15, 2004·American Journal of Respiratory Medicine : Drugs, Devices, and Other Interventions·Godfried M Roomans
Nov 18, 2000·American Journal of Physiology. Cell Physiology·L BulteauF Becq
Dec 9, 1998·The American Journal of Physiology·B IllekT E Machen
Dec 16, 1998·Archives de pédiatrie : organe officiel de la Sociéte française de pédiatrie·A ClémentG Tournier

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.