title: Decreased binding of the muscarinic antagonist [3H]N-methylscopolamine in mouse brain following acute treatment with an organophosphate.
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.
mesh_terms: D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects*; D002462:Cell Membrane / Q000378:metabolism; D066298:In Vitro Techniques; D007531:Isoflurophate / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D019832:N-Methylscopolamine; D009943:Organophosphorus Compounds / Q000494:pharmacology*; D011813:Quinuclidinyl Benzilate; D011976:Receptors, Muscarinic / Q000187:drug effects*; D012602:Scopolamine Derivatives / Q000494:pharmacology*
chemical_list: D009943:Organophosphorus Compounds; D011976:Receptors, Muscarinic; D012602:Scopolamine Derivatives; D007531:Isoflurophate; D011813:Quinuclidinyl Benzilate; D019832:N-Methylscopolamine