Lack of alterations in muscarinic receptor subtypes and phosphoinositide hydrolysis upon acute DFP treatment.
There was a 25 and 27% reduction in the density of mouse brain muscarinic acetylcholine receptors 18 and 24 h following a single injection of the organophosphate diisopropylfluorophosphate (DFP) when the muscarinic antagonist [3H]N-methylscopolamine ([3H]NMS) was used as the ligand. Down-regulation of specific [3H]NMS binding was rapidly reversible reaching control levels 36 h after DFP administration. Carbamylcholine and pirenzepine competition for the specific binding of either [3H]NMS or [3H]quinuclidinyl benzilate ([3H]QNB) in brain homogenates from untreated and DFP-treated mice demonstrated that the alteration in muscarinic receptor density following acute DFP treatment was not accompanied by a change in a particular muscarinic receptor binding conformation. Furthermore, the magnitude of muscarinic receptor-mediated phosphoinositide hydrolysis was unchanged following short-term DFP treatment suggesting that a physiological desensitization in this response does not accompany acute down-regulation of [3H]NMS binding sites.
Cioffi
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CL
Department of Pharmacology and Toxicology, University of Maryland School of Pharmacy, Baltimore 21201.
el-Fakahany
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D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects; D006868:Hydrolysis; D066298:In Vitro Techniques; D007531:Isoflurophate / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D019832:N-Methylscopolamine; D010276:Parasympatholytics / Q000494:pharmacology; D010716:Phosphatidylinositols / Q000378:metabolism*; D010890:Pirenzepine / Q000378:metabolism; D011976:Receptors, Muscarinic / Q000187:drug effects*; D012602:Scopolamine Derivatives / Q000494:pharmacology
D010276:Parasympatholytics; D010716:Phosphatidylinositols; D011976:Receptors, Muscarinic; D012602:Scopolamine Derivatives; D007531:Isoflurophate; D010890:Pirenzepine; D019832:N-Methylscopolamine