Organophosphorus insecticides induce airway hyperreactivity by decreasing neuronal M2 muscarinic receptor function independent of acetylcholinesterase inhibition

We previously demonstrated that the organophosphorus (OP) insecticide chlorpyrifos potentiates vagally induced bronchocon-striction independent of acetylcholinesterase (AChE) inhibition by decreasing the function of neuronal M2 muscarinic receptors that normally inhibit acetylcholine release from parasympathetic nerves supplying airway smooth muscle. However, it has been reported that different OPs may not affect muscarinic receptors equally. To determine if the effects of chlorpyrifos on airway hyper-reactivity can be generalized to other OPs, we tested whether para-thion and diazinon also inhibit neuronal M2 receptor function resulting in airway hyperreactivity. In control animals, the M2 agonist pilocarpine inhibits vagally induced bronchoconstriction in a dose-related manner. Treatment of guinea pigs with either para-thion (1–10 mg/kg, sc) or diazinon (0.75–75 mg/kg, sc) shifted pilo-carpine dose-response curves significantly to the right, indicatin