Modulation of lung liquid clearance by isoproterenol in rat lungs.
beta-Adrenergic agonists have been reported to increase lung liquid clearance by stimulating active Na+ transport across the alveolar epithelium. We studied mechanisms by which beta-adrenergic isoproterenol (Iso) increases lung liquid clearance in isolated perfused fluid-filled rat lungs. Iso perfused through the pulmonary circulation at concentrations of 10(-4) to 10(-8) M increased lung liquid clearance compared with that of control lungs (P < 0.01). The increase in lung liquid clearance was inhibited by the beta-antagonist propranolol (10(-5) M), the Na(+)-channel blocker amiloride (10(-4) M), and the antagonist of Na-K-ATPase, ouabain (5 x 10(-4) M). Colchicine, which inhibits cell microtubular transport of ion-transporting proteins to the plasma membrane, blocked the stimulatory effects of Iso on active Na+ transport, whereas the isomer lumicolchicine, which does not affect cell microtubular transport, did not inhibit Na+ transport. In parallel with these changes, the Na-K-ATPase alpha 1-subunit protein abundance and activity increased in alveolar type II cells stimulated by 10(-6) M Iso. Colchicine blocked the stimulatory effect of Iso and the recruitment of Na-K-ATPase alpha 1-protein to the basolateral membrane of alveolar type II cells. Accordingly, Iso increased active Na+ transport and lung liquid clearance by stimulation of beta-adrenergic receptors and probably by upregulation of apical Na+ channels and basolateral Na-K-ATPase mechanisms. Recruitment from intracellular pools and microtubular transport of Na+ pumps to the plasma membrane participate in beta-adrenergic stimulation of lung liquid clearance in rat lungs.
Saldías
F
F
Division of Pulmonary and Critical Care Medicine, Michael Reese Hospital, University of Illinois at Chicago 60616, USA.
Lecuona
E
E
Friedman
E
E
Barnard
M L
ML
Ridge
K M
KM
Sznajder
J I
JI
D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects; D001826:Body Fluids / Q000378:metabolism*; D003078:Colchicine / Q000494:pharmacology; D004848:Epithelium / Q000378:metabolism; D066298:In Vitro Techniques; D007527:Isoenzymes / Q000378:metabolism; D007545:Isoproterenol / Q000494:pharmacology*; D008162:Lumicolchicines / Q000494:pharmacology; D008168:Lung / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D010539:Permeability; D011650:Pulmonary Alveoli / Q000166:cytology / Q000187:drug effects; D051381:Rats; D012964:Sodium / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism
D000318:Adrenergic beta-Agonists; D007527:Isoenzymes; D008162:Lumicolchicines; C042109:lumicolchicine; D012964:Sodium; D000254:Sodium-Potassium-Exchanging ATPase; D007545:Isoproterenol; D003078:Colchicine