Endothelin regulation of mucus glycoprotein secretion from feline tracheal submucosal glands.
We examined the effects of endothelin on both the trichloroacetic acid precipitable 3H-labeled glycoconjugate release and intracellular Ca2+ concentration ([Ca2+]i]) measured by the usage of fura-2 in submucosal glands isolated from feline trachea. Endothelin-1 produced a significant increase in glycoconjugate release from the isolated glands in a dose-dependent fashion, reaching a response of 161% of the control at 10(-6) M. Atropine, propranolol, phentolamine, or indomethacin did not produce any significant alterations in the ET-1-evoked glycoconjugate secretion from the isolated glands. In contrast, in tracheal explants which contained epithelium, ET-1 produced a significant reduction in the glycoconjugate secretion in a dose-dependent fashion, reaching a response of 59% of the control at 10(-6) M. In the presence of cultured epithelial cells, ET-1 also produced a significant reduction in the glycoconjugate secretion from isolated glands. In isolated glands, ET-1 produced a sustained increase in the [Ca2+]i which was abolished by the removal of Ca2+ from the medium or by the presence of cultured epithelial cells. Pretreatment with indomethacin failed to alter the epithelial inhibitory action evoked by ET-1 in both the glycoconjugate secretion and the [Ca2+]i in isolated glands. ET-2 and ET-3 failed to produce significant alterations in the glycoconjugate secretion or [Ca2+]i. These findings indicate 1) that ET-1 induces mucus glycoprotein secretion via a Ca2+ influx and 2) that it possibly augments the an epithelial action inhibitory to the mucus glycoprotein secretion from airway submucosal glands.
Shimura
S
S
First Department of Internal Medicine, Tohoku University School of Medicine, Sendai, Japan.
Ishihara
H
H
Satoh
M
M
Masuda
T
T
Nagaki
N
N
Sasaki
H
H
Takishima
T
T
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002415:Cats; D000242:Cyclic AMP / Q000378:metabolism; D016232:Endothelins / Q000502:physiology*; D005088:Exocrine Glands / Q000166:cytology / Q000378:metabolism*; D006001:Glycoconjugates / Q000378:metabolism; D006023:Glycoproteins / Q000378:metabolism*; D066298:In Vitro Techniques; D007425:Intracellular Membranes / Q000378:metabolism; D009092:Mucous Membrane / Q000166:cytology / Q000378:metabolism; D009994:Osmolar Concentration; D014132:Trachea / Q000166:cytology / Q000378:metabolism*
D016232:Endothelins; D006001:Glycoconjugates; D006023:Glycoproteins; C047874:gastric mucus glycoproteins; D000242:Cyclic AMP; D002118:Calcium