Muscarinic supersensitivity and subsensitivity induced by chronic treatment with atropine and diisopropylfluorophosphate in rat submaxillary glands.

Rats were given atropine for 2 weeks and a cholinesterase inhibitor, diisopropylfluorophosphate (DFP) for 4 weeks. The secretory response of the submaxillary glands to pilocarpine and the muscarinic receptor binding to [3H]quinuclidinyl benzylate (QNB) and [3H]pirenzepine (PZ) in the submaxillary glands were investigated. Experiments were performed 48 and 24 hr after the last administration of atropine and DFP, respectively. Chronic atropine treatment enhanced the secretory response and increased the number of binding sites for [3H]QNB and [3H]PZ. The increase in number of binding sites for the 2 radioligands was almost the same. Chronic DFP treatment caused a marked decrease in the secretory response to pilocarpine, without affecting [3H]PZ and [3H]QNB binding. These results suggest that the cholinergic muscarinic M1 receptors may contribute to the development of the supersensitivity of the salivary glands caused by atropine, but not to the development of subsensitivity caused by DFP.