Irreversible Organophosphate Effects on Nicotinic Acetylcholine Receptor/Ion Channel Complex
Abstract
Organophosphate toxicity is primarily due to its inhibition of acetylcholinesterase. In sublethal doses, organophosphates induce symptoms, which cannot be solely attributed to cholinesterase inhibition, with preliminary data, indicating a direct interaction with postsynaptic nicotinic acetylcholine receptors. Membrane fragments from Torpedo electric organs were used to determine these interactions using 3H-phencyclidine as a probe. Highly toxic organophosphate agents were found to potentiate the binding of 3H-PCP to the nonactivated acetylcholine ion channel and to inhibit carbachol-activated binding. To determine the irreversibility of the effects, membrane preparations were preincubated with organophosphates and washed several times with Tris-HC1 buffer before assessing binding with 3H-PCP. Results show that organophosphates irreversibly potentiate binding. These results are consistent with the hypothesis that organophosphates bind to, and irreversibly phosphorylate, an allosteric site on the ion channel associated with the nicotinic acetylcholine receptor. Keywords: Acetylcholine receptor; Anticholinesterase; Phencyclidine; Torpedo.
Document Details
- Document Type
- Technical Report
- Publication Date
- Feb 01, 1990
- Accession Number
- ADA221073
Entities
People
- D. E. Menking
- J. J. Valdes
- R. G. Thompson
- V. L. Wolff
Organizations
- Edgewood Chemical Biological Center