OZONE-INDUCED AIRWAY HYPERRESPONSIVENESS AND LOSS OF NEURONAL M(2) MUSCARINIC RECEPTOR FUNCTION

The effect of acute ozone exposure on the function of efferent parasym pathetic nerves, M(3) muscarinic receptors on airway smooth muscle, an d inhibitory M(2) muscarinic receptors on the parasympathetic nerves w as studied. Immediately after exposure to 2.0 ppm ozone for 4 h, guine a pigs became hyperresponsive to electrical stimulation of the vagus n erves. The normal airway response to intravenous cholinergic agonists at this time demonstrates normal M(3) receptor function. M(2) muscarin ic receptors on the nerves, which normally inhibit release of acetylch oline, were dysfunctional after ozone exposure, as demonstrated by the failure of the muscarinic agonist pilocarpine to inhibit, and the fai lure of the M(2) antagonist gallamine to potentiate, vagally mediated bronchoconstriction. Thus, loss of inhibitory M(2) muscarinic receptor function after ozone exposure potentiates release of acetylcholine fr om the vagus nerves, increasing vagally mediated bronchoconstriction. By 14 days, postozone responses to vagal nerve stimulation were not di fferent from those of air-exposed animals and the function of the neur onal M(2) muscarinic receptor was normal, confirming that ozone-induce d hyperresponsiveness is reversible.