MUSCARINIC INHIBITORY AUTORECEPTORS IN DIFFERENT GENERATIONS OF HUMANAIRWAYS

The present study was undertaken to investigate the functional presenc e of inhibitory muscarinic M(2) autoreceptors on postganglionic cholin ergic nerve endings in different generations of human airways. To this end, the effects of the M(2)-selective muscarinic receptor antagonist s AQ-RA 741 and gallamine were studied on electrical field stimulation -induced twitch contractions of preparations from trachea and from bro nchial airways of varying diameter. Furthermore, electrically evoked r elease of endogenous acetylcholine from human bronchial preparations, and the effect of the muscarinic receptor antagonist atropine thereon, was measured by high-performance liquid chromatography. On average, t witch contractions were significantly but only slightly (11 to 15%) po tentiated by M(2)-selective concentrations of AQ-RA 741 and gallamine, despite approximately half of the preparations showing no potentiatio n at all. A subdivision into airway generations showed that M(2) autor eceptor function was not readily detectable in bronchioles and subsegm ental bronchi. By contrast both with AQ-RA 741 and gallamine a clear p otentiation (26 to 36%) of the twitch contractions was observed in app roximately half of the terminal bronchi and in all central airway prep arations. Moreover, the evoked release of endogenous acetylcholine in terminal and subsegmental bronchi was significantly facilitated by atr opine, to 162 to 189% of controls. These results provide strong and pa rtly direct evidence for the existence of inhibitory muscarinic M(2) r eceptors on postganglionic cholinergic nerve endings in human central airways and subsegmental and terminal bronchi, but not in bronchioli. It remains to be established, however, why these M(2) receptors exhibi t a rather variable functionality in regulating cholinergic nerve-medi ated contraction in different airway generations.