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102. , Interaction of organophosphorus compounds with muscarinic receptors in SH-SY5Y human neuroblastoma cells, J. Toxicol. Environ. Health, 43, 51, 1994. 103. S. , Organophosphate-induced alterations in muscarinic receptor binding and phosphoinositide hydrolysis in the human SK-N-SH cell line, Neurotoxicology, 13, 365, 1992. 104. , Putative M2 muscarinic receptors of rat heart have high affinity for organophosphorus anticholinesterases, Toxicol. Appl. , 103, 474, 1990. 105. , Relationship between desensitization and sequestration of muscarinic cholinergic receptors in two neuronal cell lines, Neuropharmacology, 28, 1253, 1989.

Moreover, as elucidated in the previous paragraph, differential analysis of the various stereoisomers of a nerve agent is also required. 13 –15 Although this approach affords sufficiently low minimum detectable concentrations, the separation of intact nerve agent and metabolites was based solely on liquid extraction schemes, which provide insufficient selectivity. In principle, the approach of Harris et al. 16 The relatively volatile nature of nerve agents, the extremely low detection limits of modern detectors for gas chromatography, and the recent advances in chiral separation in gas chromatography have led to the extensive use of this technique for toxicokinetic investigations of nerve agents.

Neuronal nicotinic receptors include the 108 ␣7 and the ␣4␤2 classes. 109 –111 Similar functions can be ascribed to the ␣4␤2 receptors, although their time course, particularly for desensitization, is slower. Significantly, the ␣7 receptors are activated by both acetylcholine and choline with similar sensitivity while the ␣4␤2 receptors are activated only by acetylcholine. This suggests that a decrease in the concentration of choline present due to AChE inhibition with nerve CW agents could alter the glutaminergic or GABAergic tone in regulated synapses.

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