Lack of desensitization of muscarinic receptor–mediated second messenger signals in rat brain upon acute and chronic inhibition of acetylcholinesterase

Elsayed A M Abdallah, Esam E. El‐Fakahany

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

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 downregulation 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.

Original languageEnglish (US)
Pages (from-to)261-268
Number of pages8
JournalJournal of Biochemical Toxicology
Volume6
Issue number4
DOIs
StatePublished - Jan 1 1991

Fingerprint Dive into the research topics of 'Lack of desensitization of muscarinic receptor–mediated second messenger signals in rat brain upon acute and chronic inhibition of acetylcholinesterase'. Together they form a unique fingerprint.

Cite this