Phenanthrolines--a new class of CFTR chloride channel openers

British Journal of Pharmacology
M DuszykA W Cuthbert

Abstract

1. A number of phenanthrolines and benzoquinolines were examined for their ability to activate epithelial chloride secretion by measuring short circuit current (SCC) using the mouse colon epithelium. 1,10 phenanthroline stimulated electrogenic chloride secretion with an EC(50) of 612+/-10 microM and a Hill slope of 4.9+/-0.3. A similar pharmacology was demonstrated by both 1,7 and 4,7 phenanthrolines, 7,8 benzoquinoline and phenanthridine. 2. Evidence that the increase in SCC caused by 1,10 phenanthroline was due to chloride secretion is based upon (a) inhibition of the current by furosemide, (b) failure of cystic fibrosis (CF) colons to respond and (c) an associated net flux of (36)Cl(-). 3. 1,10 Phenanthroline affected neither the generation of cyclic AMP or the concentration of intracellular Ca(2+) in colonic epithelial cells. 4. 1,10 phenanthroline affected the chloride conductance of the apical membrane, as shown by an increase in chloride current in 'apical membrane only' preparations in the presence of an apical to basolateral chloride gradient. The increase in chloride current was inhibited by 5-nitro-2-(3-phenylpropylamino) benzoic acid (NPPB) and was not present in CF colons. 5. Additionally, 1,10 phenanthroline activ...Continue Reading

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Citations

Dec 3, 2003·Current Opinion in Pharmacology·Jay R Thiagarajah, A S Verkman
Jun 1, 2005·European Journal of Pharmacology·Meena MurthyAlan Cuthbert
Nov 5, 2002·Trends in Pharmacological Sciences·Alan W Cuthbert
Feb 25, 2003·The Journal of Physiology·Rebecca S LamMarek Duszyk
Jul 23, 2003·The Journal of Physiology·A W CuthbertL J MacVinish
Jun 19, 2007·Trends in Pharmacological Sciences·Margarida D Amaral, Karl Kunzelmann
Sep 12, 2003·British Journal of Pharmacology·A W Cuthbert, L J MacVinish
May 2, 2003·British Journal of Pharmacology·Alan W Cuthbert
Apr 20, 2004·American Journal of Physiology. Lung Cellular and Molecular Physiology·S J RammingerS M Wilson
Feb 11, 2005·American Journal of Physiology. Cell Physiology·Lawrence J AlvarezOscar A Candia
Jan 15, 2004·American Journal of Respiratory Medicine : Drugs, Devices, and Other Interventions·Godfried M Roomans

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