Pre-junctional muscarinic autoreceptors in bovine airways

We searched for pre-junctional inhibitory muscarinic receptors in isolated bovine trachealis strips and bronchial rings. Electric stimulation (ES)-induced tritiated acetylcholine ([3H]-ACh)-release and isometric contractions were determined in muscles incubated with the non-selective muscarinic agonist pilocarpine, the non-selective muscarinic antagonist atropine, the selective M2-receptor antagonists methoctramine and gallamine, or the selective M4-receptor antagonist PD102807. Electric field stimulation (EFS)-induced isometric contractile responses were assessed in trachealis strips and bronchial rings treated with 10−9–10−5 M methoctramine, gallamine or PD102807. Pilocarpine (10−6 and 10−5 M) and atropine (10−7 M) significantly decreased and increased ES-evoked [3H]-ACh-release, respectively. The enhancing effect of atropine on [3H]-ACh-release prevailed over the inhibitory effect of pilocarpine. M2- and M4-receptor antagonists did not increase EFS-induced contraction or ES-induced [3H]-ACh-release. However, 10−7 M methoctramine, gallamine or PD102807 significantly attenuated the inhibitory effects of pilocarpine 10−5 M on ES-induced [3H]-ACh-release. Conclusions: Muscarinic autoregulation is present in bovine airways but is not fully accounted for by M2- and M4-receptor subtypes.

► We searched for pre-junctional muscarinic autoreceptors in isolated bovine airways. ► Pilocarpine decreased electrically evoked ACh release and atropine increased it. ► The enhancing effect of atropine prevailed over the inhibitory effect of pilocarpine. ► M2 and M4 antagonists partially attenuated the effect of pilocarpine. ► Muscarinic autoreceptors in addition to M2 and M4 may exist in bovine airways.