Related Experiment Video
Updated: Jul 11, 2026

Functional Reconstitution and Channel Activity Measurements of Purified Wildtype and Mutant CFTR Protein
Published on: March 9, 2015
Phenanthrolines--a new class of CFTR chloride channel openers
M Duszyk1, L MacVinish, A W Cuthbert
1Department of Medicine, University of Cambridge, Addenbrooke's Hospital, Hills Road, Cambridge, CB2 2QQ.
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 activated basolateral K(+) channels, both Ca(2+)- and cyclic AMP-sensitive channels, as shown by inhibitor studies with charybdotoxin (ChTX) and XE991, and after the apical membrane was permeabilized with nystatin. 6. The phenanthrolines and benzoquinolines described here, with dual actions affecting CFTR and basolateral K(+) channels, may constitute useful lead compounds for adjunct therapy in CF.
More Related Videos
07:04Forskolin-induced Swelling in Intestinal Organoids: An In Vitro Assay for Assessing Drug Response in Cystic Fibrosis Patients
Published on: February 11, 2017
06:59A Fluorescence-Based Assay of Membrane Potential for High-Throughput Functional Study of Two Endogenous Ion Channels in Two Epithelial Cell Lines
Published on: June 22, 2022
Related Concept Videos
Ligand-Gated Ion Channel Receptor: Gating Mechanism
Transducer Mechanism: Enzyme-Linked Receptors
Major types that are helpful drug targets include:
Direct-Acting Cholinergic Agonists: Therapeutic Uses
Adrenergic Agonists: Direct-Acting Agents
These agents can be classified...
Antiarrhythmic Drugs: Class I Agents as Sodium Channel Blockers
Class 1A Antiarrhythmic Drugs: These drugs work by moderately blocking sodium channels,...
Pharmacogenomics: Identification of New Drug Targets