title: Eprazinone alters lung lavage lipid levels and transtracheal ion transport.
abstract: Eprazinone therapy improves pulmonary function and arterial pO2 in patients with chronic bronchitis; however, the mechanism of action is unknown. The purpose of this study was to determine if eprazinone alters either lung surfactant levels in bronchoalveolar lavage fluid (BAL) of normal rats, or ion transport across canine tracheal epithelium mounted in Ussing chambers. In the surfactant studies, normal rats were force fed three doses (50, 100, and 200 mg/kg) of eprazinone for 4 days. Eprazinone at a dose of 200 mg/kg significantly increased total and individual (with the exception of phosphatidylinositol) phospholipid levels and decreased total neutral lipids. Lower doses of eprazinone significantly decreased neutral lipid levels without affecting the phospholipids. There was no change in BAL levels of protein or cells and no abnormal histology. In airway epithelial studies, mucosal addition of eprazinone produced a dose-dependent partially reversible decrease in short-circuit current (Isc). The decrease in Isc at lower eprazinone concentrations was accounted for entirely by a decrease in net chloride secretion while at higher concentrations both sodium and chloride transport were affected. Submucosal eprazinone had no affect on ion transport. These studies suggest that eprazinone influences both BAL lipid levels and ion transport, either of which could lead to a beneficial therapeutic effect.
authors.affiliation: Department of Medicine, University of Connecticut Health Center, Farmington 06030.
authors.forename: R S
authors.initials: RS
authors.lastname: Thrall
authors.forename: M M
authors.initials: MM
authors.lastname: Cloutier
authors.forename: L
authors.initials: L
authors.lastname: Guernsey
authors.forename: E
authors.initials: E
authors.lastname: Swayne
authors.forename: M
authors.initials: M
authors.lastname: Gionfriddo
mesh_terms: D000042:Absorption / Q000187:drug effects; D000818:Animals; D000996:Antitussive Agents / Q000494:pharmacology*; D001992:Bronchoalveolar Lavage Fluid / Q000378:metabolism*; D002712:Chlorides / Q000378:metabolism; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism; D050356:Lipid Metabolism; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D011427:Propiophenones / Q000494:pharmacology*; D011663:Pulmonary Surfactants / Q000187:drug effects; D051381:Rats; D011916:Rats, Inbred F344; D015657:Respiratory Transport / Q000187:drug effects*; D012964:Sodium / Q000378:metabolism; D014132:Trachea / Q000378:metabolism*
chemical_list: D000996:Antitussive Agents; D002712:Chlorides; D011427:Propiophenones; D011663:Pulmonary Surfactants; C007608:eprazinone; D012964:Sodium