Inhibition of the voltage-dependent chloride channel of Torpedo electric organ by diisopropylfluorophosphate and its reversal by oximes
Diisopropylfluorophosphate (DFP), a potent organophosphate inhibitor of cholinesterases, was found to inhibit the specific binding of (/sup 35/S)t-butylbicyclophosphorothionate (TBPS), specific chloride channels ligand, to the electric organ membranes of Torpedo, with a Ki of 21 +/- 3 ..mu..M. The binding sites of (/sup 35/S)TBPS in the Torpedo membranes were found not to be GABA receptors or nicotinic acetylcholine receptors as previously described. Interestingly, a stimulation of the binding of (/sup 35/S)TBPS was observed in the presence of atropine and three oximes, monopyridinium oxime 2-PAM, bispyridinium bis-oxime TMB-4 and H-oxime HI-6. The maximal stimulation was 300-500% of control, after which, the stimulation was reversed at higher concentrations. The three oximes protected by more than 95% the inhibition by 1 mM DFP of the binding of (/sup 35/S)TBPS to the voltage-dependent chloride channel. However, atropine protected only 20% of the inhibited channel. These results, thus, suggest that the protection against the toxic effects of DFP or other anticholinesterase agents by the tested oximes may not be solely a result of the reactivation of cholinesterases but also the protection of the voltage-dependent chloride channel.
- Research Organization:
- Walter Reed Army Institute of Research, Washington, DC
- OSTI ID:
- 7025264
- Report Number(s):
- CONF-8606151-
- Journal Information:
- Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States), Journal Name: Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States) Vol. 45:6; ISSN FEPRA
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
59 BASIC BIOLOGICAL SCIENCES
AMINES
ANIMALS
AQUATIC ORGANISMS
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BIOCHEMICAL REACTION KINETICS
BIOELECTRICITY
BIOLOGICAL EFFECTS
CELL CONSTITUENTS
CELL MEMBRANES
CHLORIDES
CHLORINE COMPOUNDS
DAYS LIVING RADIOISOTOPES
ELECTRICITY
ENZYME INHIBITORS
EVEN-ODD NUCLEI
FISHES
HALIDES
HALOGEN COMPOUNDS
HYDROXY COMPOUNDS
INHIBITION
ISOTOPE APPLICATIONS
ISOTOPES
KINETICS
LIGANDS
LIGHT NUCLEI
MEMBRANE PROTEINS
MEMBRANE TRANSPORT
MEMBRANES
NUCLEI
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANIC SULFUR COMPOUNDS
OXIMES
OXYGEN COMPOUNDS
PHOSPHATES
PHOSPHORUS COMPOUNDS
PROTEINS
RADIOISOTOPES
REACTION KINETICS
RECEPTORS
SULFUR 35
SULFUR ISOTOPES
THIONATES
TRACER TECHNIQUES
VERTEBRATES