title: Modulation of ion transport in cultured rabbit tracheal epithelium by lipoxygenase metabolites.
abstract: Lipoxygenase metabolites influence ion movement and fluid balance in the airways. We studied the effects of nordihydroguaiaretic acid (NDGA), a general inhibitor of the lipoxygenase pathway, on Na+ and Cl- secretion in cultured tracheal epithelial cells from adult rabbits through short-circuit current (Isc) and radioactive tracer flux experiments. NDGA inhibition of leukotriene release in freshly isolated rabbit tracheal epithelial cells was assayed by a 3H peptidyl-leukotriene radioimmunoassay. 3 microM NDGA resulted in a 91% reduction of leukotriene release. In unstimulated cultures, Cl- secretion (furosemide-inhibited fraction of Isc) was 11.1 +/- 2.8 muamp/cm2 (n = 10) and was unchanged in the presence of NDGA (n = 10). Epinephrine-stimulated Cl- secretion increased Isc by 12.2 +/- 2 muamp/cm2 (n = 10). This stimulation was unchanged by pretreatment with NDGA (n = 10), suggesting that inhibition of the lipoxygenase pathway did not affect Cl- secretion. In unstimulated cultures, Na+ absorption (amiloride-inhibited portion of Isc) was 10.7 +/- 3.3. muamp/cm2 (n = 10) and was reduced by 79% in the presence of NDGA (n = 10), suggesting that inhibition of the lipoxygenase pathway was associated with inhibition of Na+ absorption. Radioactive tracer flux experiments supported these findings. Exogenous LTD4 (n = 7) and LTC4 (n = 7) were added to cells pretreated with NDGA, and Na+ absorption was restored to 76% and 70% of control, respectively. In addition, LTD4 (n = 4) and LTC4 (n = 4) were added to cells without prior inhibition of the lipoxygenase pathway to NDGA and resulted in an increase in Cl- secretion.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Eudowood Division of Pediatric Respiratory Sciences, Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD 21205.
authors.forename: M E
authors.initials: ME
authors.lastname: Egan
authors.forename: M H
authors.initials: MH
authors.lastname: Wagner
authors.forename: P L
authors.initials: PL
authors.lastname: Zeitlin
authors.forename: W B
authors.initials: WB
authors.lastname: Guggino
mesh_terms: D000584:Amiloride / Q000494:pharmacology; D000818:Animals; D001692:Biological Transport; D002478:Cells, Cultured; D002712:Chlorides / Q000378:metabolism*; D004847:Epithelial Cells; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism; D005665:Furosemide / Q000494:pharmacology; D007477:Ions; D015289:Leukotrienes / Q000096:biosynthesis; D008084:Lipoxygenase / Q000378:metabolism*; D009637:Masoprocol / Q000494:pharmacology; D011817:Rabbits; D011863:Radioimmunoassay; D012964:Sodium / Q000378:metabolism*; D014132:Trachea / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*
chemical_list: D002712:Chlorides; D007477:Ions; D015289:Leukotrienes; D009637:Masoprocol; D000584:Amiloride; D005665:Furosemide; D012964:Sodium; D008084:Lipoxygenase