Abstract
The actions of the irreversible organophosphorus cholinesterase (ChE) inhibitor soman were investigated on canine tracheal smooth muscle in vitro. Concentrations of soman ≥ 1 nM increased the amplitude and decay of contractions elicited by electric field stimulation. The effect on decay showed a marked dependence on stimulation frequency, undergoing a 2.4-fold increase between 3 and 60 Hz. Soman also potentiated tensions due to bath applied acetylcholine (ACh). Little or no potentiation was observed for contractions elicited by carbamylcholine, an agonist that is not hydrolyzed by ChE. Concentration of soman ≥ 3 nM led to the appearance of sustained contractures. These contractures developed with a delayed onset and were well correlated with ChE activity. Alkylation of muscarinic receptors by propylbenzilylcholine mustard antagonized the actions of soman on both spontaneous and electrically-evoked muscle contractions. The results are consistent with a mechanism in which the toxic actions of soman are mediated by accumulation of neurally-released ACh secondary to inhibition of ChE activity. An important factor in this accumulation is suggested to be the buffering effect of the muscarinic receptors on the efflux of ACh from the neuroeffector junction.
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The opinions or assertions contained herein are the private views of the authors and are not to be construed as official views of the Army or the Department of Defense. In conducting the research described in this report, the investigators adhered to the “Guide for the Care and Use of Laboratory Animals” as adopted and promulgated by the National Institutes of Health
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Adler, M., Moore, D.H. & Filbert, M.G. Mechanism of soman-induced contractions in canine tracheal smooth muscle. Arch Toxicol 66, 204–210 (1992). https://doi.org/10.1007/BF01974016
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DOI: https://doi.org/10.1007/BF01974016