title: Hormonal modulation of Na(+) transport in rat fetal distal lung epithelial cells.
abstract: Isolated rat fetal distal lung epithelial (FDLE) cells were cultured (approximately 48 h) on permeable supports in medium devoid of hormones and growth factors whilst P(O2) was maintained at the level found in either the fetal (23 mmHg) or the postnatal (100 mmHg) alveolar regions. The cells became incorporated into epithelial layers that generated a basal short-circuit current (I(SC)) attributable to spontaneous Na(+) absorption. Cells at neonatal P(O2) generated larger currents than did cells at fetal P(O2), indicating that this Na(+) transport process is oxygen sensitive. Irrespective of P(O2), isoprenaline failed to elicit a discernible change in I(SC), demonstrating that beta-adrenoceptor agonists do not stimulate Na(+) transport under these conditions. However, isoprenaline did elicit cAMP accumulation in these cells, indicating that functionally coupled beta-adrenoceptors are present. Further experiments showed that isoprenaline did increase I(SC) in cells treated (24 h) with a combination of tri-iodothyronine (T(3), 10 nM) and dexamethasone (200 nM). Studies of basolaterally permeabilised cells showed that these hormones are essential for the isoprenaline-evoked increase in the apical membrane's Na(+) conductance (G(Na)), whereas isoprenaline-evoked changes in apical Cl(-) conductance (G(Cl)) can occur in both control and hormone-treated cells. Irrespective of their hormonal status, FDLE cells thus express beta-adrenoceptors that are functionally coupled to adenylate cyclase, and allow beta-adrenoceptor agonists to modulate the apical membrane's anion conductance. However, T(3) and dexamethasone are needed if these receptors are to exert control over G(Na). These hormones may thus play an important role in the functional maturation of the lung by allowing beta-adrenoceptor-mediated control over epithelial Na(+) channels in the apical plasma membrane.
authors.affiliation: Lung Membrane Transport Group, Tayside Institute of Child Health, Ninewells Hospital and Medical School, University of Dundee, Dundee DD1 9SY, Scotland, UK.
authors.forename: S J
authors.initials: SJ
authors.lastname: Ramminger
authors.forename: S K
authors.initials: SK
authors.lastname: Inglis
authors.forename: R E
authors.initials: RE
authors.lastname: Olver
authors.forename: S M
authors.initials: SM
authors.lastname: Wilson
mesh_terms: D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002478:Cells, Cultured; D002712:Chlorides / Q000502:physiology; D003470:Culture Media; D000242:Cyclic AMP / Q000096:biosynthesis; D003907:Dexamethasone / Q000494:pharmacology*; D004338:Drug Combinations; D004553:Electric Conductivity; D004848:Epithelium / Q000196:embryology; D005333:Fetus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D005938:Glucocorticoids / Q000494:pharmacology*; D007545:Isoproterenol / Q000494:pharmacology; D008168:Lung / Q000196:embryology*; D010100:Oxygen / Q000378:metabolism; D010313:Partial Pressure; D051381:Rats; D012964:Sodium / Q000502:physiology; D014284:Triiodothyronine / Q000494:pharmacology*
chemical_list: D000318:Adrenergic beta-Agonists; D002712:Chlorides; D003470:Culture Media; D004338:Drug Combinations; D005938:Glucocorticoids; D014284:Triiodothyronine; D003907:Dexamethasone; D012964:Sodium; D000242:Cyclic AMP; D007545:Isoproterenol; D010100:Oxygen; D015056:1-Methyl-3-isobutylxanthine