title: Signature current of SO2-induced bronchitis in rabbit.
abstract: To investigate abnormalities of airway epithelial ion transport underlying chronic inflammatory airway diseases, we performed electrophysiological, histological, and molecular biological experiments using rabbits exposed to SO2 as a model of bronchitis. By comparison with control, the SO2-exposed trachea exhibited decreased short circuit current (Isc) and conductance associated with increased potential difference. In normal trachea, apical ATP induced a transient Isc activation followed by a suppression, whereas the bronchitis model exhibited a prolonged activation without suppression. This pathological ATP response was abolished by diphenylamine 2-carboxylate or Cl--free bath solution. A significant increase in net Cl- flux toward the lumen was observed after ATP in our bronchitis model. Isoproterenol or adenosine evoked a sustained Isc increase in SO2-exposed, but not in normal, tracheas. The Northern blot analysis showed a strong expression of cystic fibrosis transmembrane conductance regulator (CFTR) mRNA in SO2-exposed epithelium. The immunohistochemical study revealed a positive label of CFTR on cells located luminally only in SO2-exposed rabbits. We concluded that the prolonged ATP response in our bronchitis model was of a superimposed normal and adenosine-activated current. The latter current was also activated by isoproterenol and appeared as a signature current for the bronchitis model airway. This was likely mediated by CFTR expressed in the course of chronic inflammation.
authors.affiliation: First Department of Internal Medicine, Tohoku University School of Medicine, Aoba-ku, Sendai, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Iwase
authors.forename: T
authors.initials: T
authors.lastname: Sasaki
authors.forename: S
authors.initials: S
authors.lastname: Shimura
authors.forename: T
authors.initials: T
authors.lastname: Fushimi
authors.forename: H
authors.initials: H
authors.lastname: Okayama
authors.forename: H
authors.initials: H
authors.lastname: Hoshi
authors.forename: T
authors.initials: T
authors.lastname: Irokawa
authors.forename: K
authors.initials: K
authors.lastname: Sasamori
authors.forename: K
authors.initials: K
authors.lastname: Takahashi
authors.forename: K
authors.initials: K
authors.lastname: Shirato
mesh_terms: D000241:Adenosine / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D001991:Bronchitis / Q000139:chemically induced / Q000378:metabolism*; D018118:Chloride Channels / Q000502:physiology*; D000242:Cyclic AMP / Q000502:physiology; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000032:analysis / Q000235:genetics; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D011817:Rabbits; D013458:Sulfur Dioxide / Q000633:toxicity*
chemical_list: D018118:Chloride Channels; D013458:Sulfur Dioxide; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D000255:Adenosine Triphosphate; D000242:Cyclic AMP; D000241:Adenosine; D007545:Isoproterenol