Direct inhibitory action of glucocorticoid on glycoconjugate secretion from airway submucosal glands.
The precise mechanism by which glucocorticoids inhibit airway mucus secretion is still unknown. To study directly the effect of glucocorticoid on submucosal gland secretion, we examined the effects of dexamethasone on the precursor uptake, biosynthesis, and release of mucus glycoprotein in isolated feline tracheal submucosal glands. Mucus glycoprotein release from isolated glands was estimated by measuring [3H]glucosamine-labeled trichloroacetic acid (TCA)-precipitable glycoconjugates secreted into the medium. Released glycoconjugate per hour per dry weight of gland tissue was less than 7% of the total intracellular content, where intracellular content is defined as total 3H activity in the dissolved gland tissue. Treatment with 10(-9) to 10(-5) M dexamethasone for 24 to 72 h significantly reduced basal glycoconjugate secretion up to 22% of control (a 78% decrease) in a dose-dependent fashion, whereas the total intracellular 3H content was reduced to 70% of control (a 30% decrease) with no statistically significant differences from controls. The ratio of released glycoconjugates to the total intracellular content decreased significantly to 31% of control (a 69% decrease) after the treatment with 10(-10) to 10(-5) M dexamethasone. Further, ratio of radioactivity of TCA-precipitable glycoconjugates in the dissolved gland tissue to the total intracellular 3H content increased from 40% in nontreated controls to 46% after the treatment with dexamethasone (10(-5) M). Dexamethasone also inhibited the glycoconjugate secretion stimulated by dibutyryl cyclic AMP and alpha- and beta-adrenergic agonists. Simultaneously, the ratio of released to total intracellular content also decreased significantly after dexamethasone treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
Shimura
S
S
First Department of Internal Medicine, Tohoku University School of Medicine, Sendai, Japan.
Sasaki
T
T
Ikeda
K
K
Yamauchi
K
K
Sasaki
H
H
Takishima
T
T
D000818:Animals; D001285:Atropine / Q000494:pharmacology; D003994:Bucladesine / Q000037:antagonists & inhibitors; D002415:Cats; D003907:Dexamethasone / Q000494:pharmacology*; D005280:Fenoterol / Q000494:pharmacology; D006001:Glycoconjugates / Q000378:metabolism*; D066298:In Vitro Techniques; D016210:Methacholine Chloride; D008688:Methacholine Compounds; D009093:Mucus / Q000378:metabolism*; D010656:Phenylephrine / Q000037:antagonists & inhibitors; D014132:Trachea / Q000187:drug effects / Q000378:metabolism*
D006001:Glycoconjugates; D008688:Methacholine Compounds; D016210:Methacholine Chloride; D010656:Phenylephrine; D005280:Fenoterol; D003994:Bucladesine; D001285:Atropine; D003907:Dexamethasone