Decreased binding of the muscarinic antagonist [3H]N-methylscopolamine in mouse brain following acute treatment with an organophosphate

Catherine L. Cioffi, Esam E. El-Fakahany

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17 Scopus citations

Abstract

The effect of the irreversible acetylcholinesterase inhibitor diisopropylfluorophosphate (DFP) on mouse brain muscarinic acetylcholine receptors was assessed using the muscarinic antagonists [3H]N-methylscopolamine ([3H]NMS) and [3H]quinuclidinyl benzilate ([3H]QNB). No alteration in the maximal binding capacity (Bmax) or equilibrium dissociation constant (KD) was observed in brain homogenates obtained from mice 12 h after a single injection of DFP when [3H]NMS was employed as the ligand. However, one administration of DFP produced a 24 and 33% decrease in Bmax as measured by [3H]NMS binding after 18 and 24 h, respectively. A similar decrease in Bmax was found after two (31%) and three (29%) days of daily DFP treatment. On the other hand, Scatchard analysis using [3H]QNB binding in the brain revealed no difference in KD or Bmax between untreated and 24 h DFP-treated mice. Thus, there is a differential alteration in mouse brain muscarinic acetylcholine receptors using these two ligands which suggests that [3H]NMS binding sites are more sensitive to regulation following acute organophosphate administration.

Original languageEnglish (US)
Pages (from-to)147-154
Number of pages8
JournalEuropean Journal of Pharmacology
Volume132
Issue number2-3
DOIs
StatePublished - Dec 16 1986

Bibliographical note

Funding Information:
* Supported by a contract from the U.S. Army Research Office (DAAG-29-85-K-0123). * Recipient of a Research Career Development Award from the National Institutes of Health (AG-00344). To whom all correspondence should be addressed,

Keywords

  • Desensitization
  • Diisopropylfluorophosphate
  • Down-regulation
  • Muscarinic receptors
  • Organophosphate
  • Tolerance

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