Lack of alterations in muscarinic receptor subtypes and phosphoinositide hydrolysis upon acute DFP treatment

Abstract

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.