Loop diuretics are open‐channel blockers of the cystic fibrosis transmembrane conductance regulator with distinct kinetics

Loop diuretics are widely used to inhibit the Na+, K+, 2Cl− co‐transporter, but they also inhibit the cystic fibrosis transmembrane conductance regulator (CFTR) Cl− channel. Here, we investigated the mechanism of CFTR inhibition by loop diuretics and explored the effects of chemical structure on channel blockade.

[1]  Adam J Pawson,et al.  The Concise Guide to Pharmacology 2013/14: Overview , 2013, British journal of pharmacology.

[2]  D. Sheppard,et al.  Acute inhibition of the cystic fibrosis transmembrane conductance regulator (CFTR) Cl- channel by thyroid hormones involves multiple mechanisms. , 2013, American journal of physiology. Cell physiology.

[3]  L. Frye,et al.  Locating a Plausible Binding Site for an Open-Channel Blocker, GlyH-101, in the Pore of the Cystic Fibrosis Transmembrane Conductance Regulator , 2012, Molecular Pharmacology.

[4]  Jordi Villà-Freixa,et al.  New Model of Cystic Fibrosis Transmembrane Conductance Regulator Proposes Active Channel-like Conformation , 2012, J. Chem. Inf. Model..

[5]  Anthony Ivetac,et al.  Cystic fibrosis transmembrane conductance regulator: a molecular model defines the architecture of the anion conduction path and locates a "bottleneck" in the pore. , 2012, Biochemistry.

[6]  N. McCarty,et al.  Differential contribution of TM6 and TM12 to the pore of CFTR identified by three sulfonylurea-based blockers , 2011, Pflügers Archiv - European Journal of Physiology.

[7]  Tzyh-Chang Hwang,et al.  On the mechanism of CFTR inhibition by a thiazolidinone derivative , 2010, The Journal of general physiology.

[8]  P. Linsdell,et al.  Changes in Accessibility of Cytoplasmic Substances to the Pore Associated with Activation of the Cystic Fibrosis Transmembrane Conductance Regulator Chloride Channel* , 2010, The Journal of Biological Chemistry.

[9]  D. Sheppard,et al.  Direct Sensing of Intracellular pH by the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Cl− Channel*♦ , 2009, The Journal of Biological Chemistry.

[10]  Wen Ying Chen,et al.  The cystic fibrosis transmembrane conductance regulator in reproductive health and disease , 2009, The Journal of physiology.

[11]  Alan S. Verkman,et al.  Chloride channels as drug targets , 2009, Nature Reviews Drug Discovery.

[12]  M. Amaral,et al.  Prolonged treatment of cells with genistein modulates the expression and function of the cystic fibrosis transmembrane conductance regulator , 2008, British journal of pharmacology.

[13]  Christopher H. Thompson,et al.  State-dependent Inhibition of Cystic Fibrosis Transmembrane Conductance Regulator Chloride Channels by a Novel Peptide Toxin* , 2007, Journal of Biological Chemistry.

[14]  P. Linsdell,et al.  Identification of a Second Blocker Binding Site at the Cytoplasmic Mouth of the Cystic Fibrosis Transmembrane Conductance Regulator Chloride Channel Pore , 2007, Molecular Pharmacology.

[15]  N. Vázquez,et al.  Activity of the renal Na+-K+-2Cl- cotransporter is reduced by mutagenesis of N-glycosylation sites: role for protein surface charge in Cl- transport. , 2006, American journal of physiology. Renal physiology.

[16]  Paola Vergani,et al.  The ABC protein turned chloride channel whose failure causes cystic fibrosis , 2006, Nature.

[17]  A. Taddei,et al.  Differential Sensitivity of the Cystic Fibrosis (CF)-associated Mutants G551D and G1349D to Potentiators of the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Cl– Channel* , 2006, Journal of Biological Chemistry.

[18]  J. Clancy,et al.  Activating Cystic Fibrosis Transmembrane Conductance Regulator Channels with Pore Blocker Analogs* , 2005, Journal of Biological Chemistry.

[19]  P. Linsdell,et al.  Location of a Common Inhibitor Binding Site in the Cytoplasmic Vestibule of the Cystic Fibrosis Transmembrane Conductance Regulator Chloride Channel Pore* , 2005, Journal of Biological Chemistry.

[20]  David N Sheppard,et al.  The relationship between cell proliferation, Cl- secretion, and renal cyst growth: a study using CFTR inhibitors. , 2004, Kidney international.

[21]  N. McCarty,et al.  Time-dependent Interactions of Glibenclamide with CFTR: Kinetically Complex Block of Macroscopic Currents , 2004, The Journal of Membrane Biology.

[22]  D. Sheppard.  CFTR Channel Pharmacology , 2004, The Journal of general physiology.

[23]  A. Taddei,et al.  Discovery of Glycine Hydrazide Pore-occluding CFTR Inhibitors , 2004, The Journal of general physiology.

[24]  N. McCarty,et al.  Steady-State Interactions of Glibenclamide with CFTR: Evidence for Multiple Sites in the Pore , 2004, The Journal of Membrane Biology.

[25]  D. Mount,et al.  Molecular physiology of cation-coupled Cl− cotransport: the SLC12 family , 2004, Pflügers Archiv.

[26]  J. R. Torres-Lapasió,et al.  Effects of pH and the presence of micelles on the resolution of diuretics by reversed-phase liquid chromatography. , 2004, Journal of chromatography. A.

[27]  Z. Cai,et al.  Direct block of the cystic fibrosis transmembrane conductance regulator Cl− channel by niflumic acid , 2004, Molecular membrane biology.

[28]  Xuehong Liu,et al.  CFTR: what's it like inside the pore? , 2003, Journal of experimental zoology. Part A, Comparative experimental biology.

[29]  D. Sheppard,et al.  Voltage-dependent Gating of the Cystic Fibrosis Transmembrane Conductance Regulator Cl− Channel , 2003, The Journal of general physiology.

[30]  Hong Yang,et al.  Thiazolidinone CFTR inhibitor identified by high-throughput screening blocks cholera toxin-induced intestinal fluid secretion. , 2002, The Journal of clinical investigation.

[31]  P. Linsdell,et al.  Mechanism of lonidamine inhibition of the CFTR chloride channel , 2002, British journal of pharmacology.

[32]  T. Hwang,et al.  Probing an Open CFTR Pore with Organic Anion Blockers , 2002, The Journal of general physiology.

[33]  C. Folli,et al.  Correction of G551D‐CFTR transport defect in epithelial monolayers by genistein but not by CPX or MPB‐07 , 2002, British journal of pharmacology.

[34]  M. Amaral,et al.  The human DnaJ homologue (Hdj)-1/heat-shock protein (Hsp) 40 co-chaperone is required for the in vivo stabilization of the cystic fibrosis transmembrane conductance regulator by Hsp70. , 2002, The Biochemical journal.

[35]  D. Sheppard,et al.  Phloxine B Interacts with the Cystic Fibrosis Transmembrane Conductance Regulator at Multiple Sites to Modulate Channel Activity* 210 , 2002, The Journal of Biological Chemistry.

[36]  P. Hannaert,et al.  Rat NKCC2/NKCC1 cotransporter selectivity for loop diuretic drugs , 2002, Naunyn-Schmiedeberg's Archives of Pharmacology.

[37]  T. Hwang,et al.  Voltage‐dependent flickery block of an open cystic fibrosis transmembrane conductance regulator (CFTR) channel pore , 2001, The Journal of physiology.

[38]  N. McCarty,et al.  Direct Comparison of NPPB and DPC as Probes of CFTR Expressed in Xenopus Oocytes , 2000, The Journal of Membrane Biology.

[39]  U. Quast,et al.  Potent inhibition of the CFTR chloride channel by suramin , 1999, Naunyn-Schmiedeberg's Archives of Pharmacology.

[40]  Z. Cai,et al.  Inhibition of heterologously expressed cystic fibrosis transmembrane conductance regulator Cl− channels by non‐sulphonylurea hypoglycaemic agents , 1999, British journal of pharmacology.

[41]  B. Forbush,et al.  Mutagenic Mapping of the Na-K-Cl Cotransporter for Domains Involved in Ion Transport and Bumetanide Binding , 1998, The Journal of general physiology.

[42]  B. Forbush,et al.  The role of transmembrane domain 2 in cation transport by the Na-K-Cl cotransporter. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[43]  B. Forbush,et al.  Ion and Bumetanide Binding by the Na-K-Cl Cotransporter , 1997, The Journal of Biological Chemistry.

[44]  D. Sheppard,et al.  Mechanism of Glibenclamide Inhibition of Cystic Fibrosis Transmembrane Conductance Regulator Cl− Channels Expressed in a Murine Cell Line , 1997, The Journal of physiology.

[45]  A. K. Singh,et al.  Glibenclamide blockade of CFTR chloride channels. , 1996, The American journal of physiology.

[46]  A. K. Singh,et al.  Tolbutamide causes open channel blockade of cystic fibrosis transmembrane conductance regulator Cl- channels. , 1996, Biophysical journal.

[47]  J. Inazawa,et al.  Reconstitution of IKATP: An Inward Rectifier Subunit Plus the Sulfonylurea Receptor , 1995, Science.

[48]  S. Gullans,et al.  Molecular cloning and chromosome localization of a putative basolateral Na(+)-K(+)-2Cl- cotransporter from mouse inner medullary collecting duct (mIMCD-3) cells. , 1994, The Journal of biological chemistry.

[49]  M. Welsh,et al.  Effect of ATP concentration on CFTR Cl- channels: a kinetic analysis of channel regulation. , 1994, Biophysical journal.

[50]  M. Welsh,et al.  Expression of cystic fibrosis transmembrane conductance regulator in a model epithelium. , 1994, The American journal of physiology.

[51]  M. Welsh,et al.  Stoichiometry of recombinant cystic fibrosis transmembrane conductance regulator in epithelial cells and its functional reconstitution into cells in vitro. , 1994, The Journal of biological chemistry.

[52]  R. Greger,et al.  Chemical probes for anion transporters of mammalian cell membranes. , 1992, The American journal of physiology.

[53]  B. Forbush,et al.  [3H]bumetanide binding to membranes isolated from dog kidney outer medulla. Relationship to the Na,K,Cl co-transport system. , 1983, The Journal of biological chemistry.

[54]  T. McManus,et al.  Bumetanide inhibits (Na + K + 2Cl) co-transport at a chloride site. , 1983, The American journal of physiology.

[55]  R. Greger,et al.  Effect of “high ceiling” diuretics on active salt transport in the cortical thick ascending limb of Henle's loop of rabbit kidney , 1983, Pflügers Archiv.

[56]  J. H. Ludens.  Nature of the inhibition of Cl- transport by furosemide: evidence for competitive inhibition of active transport in toad cornea. , 1982, The Journal of pharmacology and experimental therapeutics.

[57]  A. Woodhull,et al.  Ionic Blockage of Sodium Channels in Nerve , 1973, The Journal of general physiology.

[58]  D. Sheppard,et al.  Therapeutic Potential of Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Inhibitors in Polycystic Kidney Disease , 2012, BioDrugs.

[59]  Karl Kuchler,et al.  ABC proteins : from bacteria to man , 2003 .

[60]  J. Russell.  Sodium-potassium-chloride cotransport. , 2000, Physiological reviews.

[61]  M. Haas,et al.  The Na-K-Cl cotransporter of secretory epithelia. , 2000, Annual review of physiology.

[62]  P. Quinton,et al.  Bumetanide blocks CFTR G Cl in the native sweat duct. , 1999, American journal of physiology. Cell physiology.

[63]  J. Riordan.  Identification of the cystic fibrosis gene: Cloning and characterization of complementary DNA , 1989 .

[64]  J. Weber,et al.  Xipamid, a potent new diuretic. , 1975, Current medical research and opinion.