Postganglionic muscarinic inhibitory receptors in pulmonary parasympathetic nerves in the guinea-pig.

Abstract

The location of neuronal inhibitory muscarinic receptors in pulmonary parasympathetic nerves was investigated in vivo and in vitro. The effects of an agonist for neuronal muscarinic receptors (pilocarpine) and an antagonist (gallamine) were tested on contractions of airway smooth muscle induced by pre- and postganglionic cholinergic nerve stimulation. In anaesthetized guinea-pigs, gallamine potentiated constriction of the tracheal tube and smaller airways induced by preganglionic stimulation. Gallamine also potentiated postganglionic stimulation induced by transmural stimulation of the tracheal tube and by 1-1-dimethyl-4-phenylpiperazinium iodide in the rest of the lung. Bronchoconstriction and contraction of the tracheal tube induced by intravenous acetylcholine were not potentiated by gallamine, indicating that postjunctional muscarinic receptors in airway smooth muscle were not involved in the potentiation. The muscarinic agonist, pilocarpine, had the opposite effect to gallamine and inhibited contractions of the tracheal tube induced by both types of nerve stimulation. In vitro, the inhibitory effect of pilocarpine was demonstrated in the tracheal tube preparation stimulated both pre- and postganglionically. The effect of pilocarpine was antagonized by gallamine. Because gallamine and pilocarpine affected the responses to postganglionic stimulation, the inhibitory muscarinic receptors must be located on the postganglionic neurones of the parasympathetic nerves innervating the trachea and the smaller airways. However, these experiments cannot exclude the possibility that muscarinic receptors may also be located on the soma of the ganglion cells.