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We studied the effects of acute and chronic in vivo inhibition of acetylcholinesterase on both the density and function of brain muscarinic cholinergic receptors. Adult male rats were treated either once or multiple times over a period of 10 days with the irreversible acetylcholinesterase inhibitor diisopropylfluorophosphate (DFP). The concentration and affinity of muscarinic receptors in various brain regions were determined using radioligand binding techniques. Acute DFP treatment resulted in a significant reduction in receptor number only in the brain stem, while chronic treatment caused receptor down-regulation in the brain stem, cerebral cortex, and striatum. There was no change in ligand affinity in any of the brain regions. In sharp contrast, muscarinic receptor function was fully preserved, in terms of coupling of the receptors to increased phosphoinositide hydrolysis in the cerebral cortex, hippocampus, and striatum, or inhibition of cyclic AMP formation in the cerebral cortex or striatum. Therefore, there is a marked lack or correlation between DFP-induced muscarinic receptor down-regulation and receptor desensitization.
E A Abdallah, and
E E el-Fakahany
May 1984,
Journal of neurochemistry,
E A Abdallah, and
E E el-Fakahany
December 1987,
The Journal of neuroscience : the official journal of the Society for Neuroscience,
E A Abdallah, and
E E el-Fakahany
August 2004,
Molecular and cellular endocrinology,
E A Abdallah, and
E E el-Fakahany
February 2007,
Toxicology and industrial health,
E A Abdallah, and
E E el-Fakahany
February 1994,
Synapse (New York, N.Y.),
E A Abdallah, and
E E el-Fakahany
January 1990,
Neurochemistry international,
E A Abdallah, and
E E el-Fakahany
October 1988,
European journal of pharmacology,
E A Abdallah, and
E E el-Fakahany
February 1993,
Neuroscience letters,
E A Abdallah, and
E E el-Fakahany
December 1989,
The Journal of pharmacology and experimental therapeutics,
E A Abdallah, and
E E el-Fakahany
October 1991,
Molecular pharmacology,
