Muscarinic receptors and parasympathetic neurotransmission in guinea-pig trachea

Muscarinic receptors involved in cholinergic neurotransmission were studied in isolated innervated guinea-pig tracheas using preganglionic (nerve) and postaganglionic (field) stimulation, after blocking sympathetic effects with bethanidine (5 μM). Neostigmine (10 nM) significantly increased responses to nerve and field stimulation. The M 1 antagonist pirenzepine (0.1–100 nM) selectively reduced tracheal responses to nerve stimulation in control and in neostigmine-treated tissues. The M 2 antagonist gallamine (0.1–100 μM) significantly increased tracheal responses to nerve and field stimulation in control and in neostigmine-treated preparations. At concentrations that increased baseline tone, oxotremorine, arecoline and pilocarpine decreased responses to nerve and field stimulation. Gallamine (30 μM) selectively reduced the inhibitory effects of these agonists on responses to nerve and field stimulation. The findings indicate that cholinergic neurotransmission in guinea-pig trachea is modulated by facilitatory M 1 receptors at parasympathetic ganglia and inhibitory M 2 receptors at the postganglionic nerve endings.