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.
- Di-isopropylfluorophosphate (DFP)
- Muscarinic acetylcholine receptor subtypes
- Phosphoinositide metabolism