Effect of soman and sarin on phosphatidylcholine asymmetry in the electroplax from the electric eel.
Some effects of organophosphorus anticholinesterase compounds that are unrelated to cholinesterase inhibition and that are sometimes long lasting may be due to alterations at the cellular membrane level. Phosphatidylcholine exchange protein was used to assess the effects of sarin and soman on phosphatidylcholine asymmetry in the inner and outer leaflets of the plasma membrane bilayer of the electroplax. Exposure of electroplax (30 min in vitro) to soman (10(-4), 10(-6) M) or sarin (10(-4), 10(-6), 5 x 10(-9) M) increased the percentage of phosphatidylcholine in the outer monolayer of the innervated plasma membrane bilayer and decreased the percentage in the inner monolayer. These changes by sarin were observed at concentrations that produced 100% cholinesterase inhibition (10(-4), 10(-6) M) and at a concentration (5 x 10(-9) M) where no inhibition occurred, suggesting that these effects are not directly due to cholinesterase inhibition. A 1-week exposure of live eels to soman (10(-8) M) in vivo caused an increase in phosphatidylcholine labeling in the outer monolayer of the innervated and noninnervated surfaces of the electroplax. Two weeks after stopping exposure to soman, increased labeling was still observed, suggesting that this may be a long-term effect. Because the organophosphates did not increase the permeability of the electroplax, all of these changes in labeling appear to be due to a redistribution of phosphatidylcholine from the inner to the outer monolayer of the plasma membrane bilayer.
Supernovich
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C
Section of Pharmacology and Toxicology, School of Pharmacy, University of Connecticut, Storrs 06269.
Crain
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R
Rosenberg
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P
D000818:Animals; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002784:Cholesterol / Q000378:metabolism; D004557:Electric Organ / Q000187:drug effects / Q000378:metabolism*; D004593:Electrophorus; D007700:Kinetics; D008051:Lipid Bilayers; D008563:Membrane Lipids / Q000378:metabolism*; D010713:Phosphatidylcholines / Q000378:metabolism*; D012524:Sarin / Q000494:pharmacology*; D012999:Soman / Q000494:pharmacology*
D008051:Lipid Bilayers; D008563:Membrane Lipids; D010713:Phosphatidylcholines; D012999:Soman; D002784:Cholesterol; D012524:Sarin