Ozone-induced airway hyperresponsiveness and loss of neuronal M2 muscarinic receptor function.
The effect of acute ozone exposure on the function of efferent parasympathetic nerves, M3 muscarinic receptors on airway smooth muscle, and inhibitory M2 muscarinic receptors on the parasympathetic nerves was studied. Immediately after exposure to 2.0 ppm ozone for 4 h, guinea pigs became hyperresponsive to electrical stimulation of the vagus nerves. The normal airway response to intravenous cholinergic agonists at this time demonstrates normal M3 receptor function. M2 muscarinic receptors on the nerves, which normally inhibit release of acetylcholine, were dysfunctional after ozone exposure, as demonstrated by the failure of the muscarinic agonist pilocarpine to inhibit, and the failure of the M2 antagonist gallamine to potentiate, vagally mediated bronchoconstriction. Thus, loss of inhibitory M2 muscarinic receptor function after ozone exposure potentiates release of acetylcholine from the vagus nerves, increasing vagally mediated bronchoconstriction. By 14 days, postozone responses to vagal nerve stimulation were not different from those of air-exposed animals and the function of the neuronal M2 muscarinic receptor was normal, confirming that ozone-induced hyperresponsiveness is reversible.
Schultheis
A H
AH
Department of Environmental Health Sciences, School of Hygiene and Public Health, Johns Hopkins University, Baltimore, Maryland 21205.
Bassett
D J
DJ
Fryer
A D
AD
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D016535:Bronchial Hyperreactivity / Q000139:chemically induced* / Q000503:physiopathology; D004558:Electric Stimulation; D005703:Gallamine Triethiodide / Q000494:pharmacology; D006145:Guanethidine / Q000494:pharmacology; D006168:Guinea Pigs; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D008688:Methacholine Compounds / Q000494:pharmacology; D009130:Muscle, Smooth / Q000187:drug effects; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D010126:Ozone / Q000633:toxicity*; D010275:Parasympathetic Nervous System / Q000187:drug effects / Q000502:physiology; D010862:Pilocarpine / Q000494:pharmacology; D011976:Receptors, Muscarinic / Q000187:drug effects*; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000502:physiology; D014630:Vagus Nerve / Q000187:drug effects / Q000502:physiology
D008688:Methacholine Compounds; D011976:Receptors, Muscarinic; D010862:Pilocarpine; D010126:Ozone; D000109:Acetylcholine; D005703:Gallamine Triethiodide; D006145:Guanethidine