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Br J Pharmacol
2000 Oct 01;1313:433-40. doi: 10.1038/sj.bjp.0703600.
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Potent stimulation and inhibition of the CFTR Cl(-) current by phloxine B.
Bachmann A
,
Russ U
,
Waldegger S
,
Quast U
.
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The effects of the fluoresceine derivative, phloxine B, on the Cl(-) current through the cystic fibrosis transmembrane conductance regulator (CFTR) were examined in Xenopus oocytes expressing human CFTR. In whole oocytes, the CFTR Cl(-) current (I(CFTR)) was activated by superfusion with isobutylmethylxanthine and forskolin. I(CFTR) was stable during activation and deactivated rapidly upon washout of the activation solution. Phloxine B slowed deactivation and, at high concentrations, inhibited I(CFTR) weakly. In excised inside-out macropatches, I(CFTR) was activated by the catalytic subunit of protein kinase A (cPKA) and MgATP. Phloxine B (0.01 - 3 microM), applied after activation, increased I(CFTR) within 30 s followed by a slow decrease which became dominant at high concentrations. Slowing of deactivation of the CFTR was observed at all concentrations. The effect of phloxine B after 30 s had a bell-shaped concentration-dependence with midpoints at 45 and 1600 nM for the stimulatory and the inhibitory limb, respectively; maximum stimulation was about 1.8 times. The slow inhibitory component, measured after 6 min, occurred with an IC(50) value of approximately 1 microM. In the absence of cPKA, phloxine B did not stimulate I(CFTR). In the presence of cPKA and MgATP, the effects of phloxine B were more prominent at low (0.02 mM) than at high ATP (2 mM). The data show that phloxine B modulates I(CFTR) by increasing channel activity and slowing channel deactivation; at high concentrations inhibition dominates. The effects may be mediated by direct interactions with CFTR from the inside of the cell.
Aguilar-Bryan,
Molecular biology of adenosine triphosphate-sensitive potassium channels.
1999, Pubmed
Aguilar-Bryan,
Molecular biology of adenosine triphosphate-sensitive potassium channels.
1999,
Pubmed
Aguilar-Bryan,
Cloning of the beta cell high-affinity sulfonylurea receptor: a regulator of insulin secretion.
1995,
Pubmed
Akiyama,
Use and specificity of genistein as inhibitor of protein-tyrosine kinases.
1991,
Pubmed
Anderson,
Nucleoside triphosphates are required to open the CFTR chloride channel.
1991,
Pubmed
Ashcroft,
Properties and functions of ATP-sensitive K-channels.
1990,
Pubmed
Ashcroft,
Correlating structure and function in ATP-sensitive K+ channels.
1998,
Pubmed
Bachmann,
Potent inhibition of the CFTR chloride channel by suramin.
1999,
Pubmed
,
Xenbase
Baukrowitz,
Coupling of CFTR Cl- channel gating to an ATP hydrolysis cycle.
1994,
Pubmed
Bear,
Cl- channel activity in Xenopus oocytes expressing the cystic fibrosis gene.
1991,
Pubmed
,
Xenbase
Bear,
Purification and functional reconstitution of the cystic fibrosis transmembrane conductance regulator (CFTR).
1992,
Pubmed
Cheng,
Phosphorylation of the R domain by cAMP-dependent protein kinase regulates the CFTR chloride channel.
1991,
Pubmed
Christopoulos,
Assessing the distribution of parameters in models of ligand-receptor interaction: to log or not to log.
1998,
Pubmed
Dickinson,
Nucleotide regulation and characteristics of potassium channel opener binding to skeletal muscle membranes.
1997,
Pubmed
Drumm,
Chloride conductance expressed by delta F508 and other mutant CFTRs in Xenopus oocytes.
1991,
Pubmed
,
Xenbase
Edwards,
The pharmacology of ATP-sensitive potassium channels.
1993,
Pubmed
Gabriel,
Cystic fibrosis heterozygote resistance to cholera toxin in the cystic fibrosis mouse model.
1994,
Pubmed
Gadsby,
Control of CFTR channel gating by phosphorylation and nucleotide hydrolysis.
1999,
Pubmed
Gatto,
Eosin, a potent inhibitor of the plasma membrane Ca pump, does not inhibit the cardiac Na-Ca exchanger.
1995,
Pubmed
Gribble,
Properties of cloned ATP-sensitive K+ currents expressed in Xenopus oocytes.
1997,
Pubmed
,
Xenbase
HODGKIN,
Measurement of current-voltage relations in the membrane of the giant axon of Loligo.
1952,
Pubmed
Hamill,
Improved patch-clamp techniques for high-resolution current recording from cells and cell-free membrane patches.
1981,
Pubmed
Hipper,
Mutations in the putative pore-forming domain of CFTR do not change anion selectivity of the cAMP activated Cl- conductance.
1995,
Pubmed
,
Xenbase
Hwang,
Molecular pharmacology of the CFTR Cl- channel.
1999,
Pubmed
Hwang,
Regulation of the gating of cystic fibrosis transmembrane conductance regulator C1 channels by phosphorylation and ATP hydrolysis.
1994,
Pubmed
Illek,
cAMP-independent activation of CFTR Cl channels by the tyrosine kinase inhibitor genistein.
1995,
Pubmed
Lansdell,
Two mechanisms of genistein inhibition of cystic fibrosis transmembrane conductance regulator Cl- channels expressed in murine cell line.
2000,
Pubmed
Löffler-Walz,
Binding of K(ATP) channel modulators in rat cardiac membranes.
1998,
Pubmed
Prince,
The CFTR advantage--capitalizing on a quirk of fate.
1998,
Pubmed
Reenstra,
CFTR chloride channel activation by genistein: the role of serine/threonine protein phosphatases.
1996,
Pubmed
Riordan,
Identification of the cystic fibrosis gene: cloning and characterization of complementary DNA.
1989,
Pubmed
Schultz,
Pharmacology of CFTR chloride channel activity.
1999,
Pubmed
Schwanstecher,
Interaction of fluorescein derivatives with sulfonylurea binding in insulin-secreting cells.
1995,
Pubmed
Schwiebert,
CFTR is a conductance regulator as well as a chloride channel.
1999,
Pubmed
Seino,
ATP-sensitive potassium channels: a model of heteromultimeric potassium channel/receptor assemblies.
1999,
Pubmed
Sheppard,
Effect of ATP-sensitive K+ channel regulators on cystic fibrosis transmembrane conductance regulator chloride currents.
1992,
Pubmed
Sheppard,
Structure and function of the CFTR chloride channel.
1999,
Pubmed
Tusnády,
Membrane topology distinguishes a subfamily of the ATP-binding cassette (ABC) transporters.
1997,
Pubmed
Wang,
Actions of genistein on cystic fibrosis transmembrane conductance regulator channel gating. Evidence for two binding sites with opposite effects.
1998,
Pubmed
Weinreich,
Direct action of genistein on CFTR.
1997,
Pubmed
,
Xenbase
Weinreich,
Dual effects of ADP and adenylylimidodiphosphate on CFTR channel kinetics show binding to two different nucleotide binding sites.
1999,
Pubmed
,
Xenbase
Welsh,
Molecular mechanisms of CFTR chloride channel dysfunction in cystic fibrosis.
1993,
Pubmed
Yang,
Modulation of CFTR chloride channels by calyculin A and genistein.
1997,
Pubmed
de Weille,
Activation and inhibition of ATP-sensitive K+ channels by fluorescein derivatives.
1992,
Pubmed