Effects of ozone on the cholinergic secretory responsiveness of ferret tracheal glands.
Oxidant air pollutants exacerbate several pulmonary diseases. Inhalation of ozone has been shown to induce airway smooth muscle hyperresponsiveness. Oxidant injury could also affect airway secretory mechanisms. We postulated that oxidant exposure would alter the glycoconjugate secretory function of airway submucosal glands. To test this hypothesis we examined the effects of in vivo ozone exposure on the in vitro secretory responsiveness of ferret tracheal glands. Ferrets were exposed to 1 ppm ozone, 24 hr/day for 3 or 7 days. Following exposure, glandular explants, denuded of surface epithelial cells, were prepared and incubated in medium containing 3H-glucosamine for 18 hr. Basal secretion of labeled glycoconjugates was significantly increased 31% following 3 days of ozone exposure (P less than or equal to 0.05) and remained elevated 11% after 7 days of exposure compared to the air-exposed group. After 3 or 7 days of exposure to ozone, tracheal gland responsiveness to carbachol was increased as indicated by significantly lower EC50 values (log molar concentration) of -6.43 +/- 0.04 (n = 6) and -6.50 +/- 0.11 (n = 5), respectively; compared to -6.20 +/- 0.08 (n = 6) for the air-exposed group. There was no difference in carbachol EC50 values for air and 7-day ozone-exposed animals treated with dexamethasone. Dexamethasone did not attenuate the ozone-induced increase in basal secretion. Tracheal gland responsiveness to alpha- or beta-adrenergic agonists was not changed by oxidant exposure. These experiments suggest that oxidant injury not only increases basal secretion of respiratory glycoconjugates but also increases tracheal gland sensitivity to a cholinergic agonist.
McBride
R K
RK
Department of Medicine, University of Rochester School of Medicine and Dentistry, New York 14642-8692.
Oberdoerster
G
G
Marin
M G
MG
D000818:Animals; D002217:Carbachol / Q000494:pharmacology; D046508:Culture Techniques; D003907:Dexamethasone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005088:Exocrine Glands / Q000187:drug effects* / Q000378:metabolism; D005289:Ferrets; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009752:Nutritional Status; D010126:Ozone / Q000633:toxicity*; D010656:Phenylephrine / Q000494:pharmacology; D014132:Trachea / Q000187:drug effects* / Q000378:metabolism
D010656:Phenylephrine; D010126:Ozone; D003907:Dexamethasone; D002217:Carbachol; D007545:Isoproterenol