Long-term terbutaline exposure stimulates alpha1-Na+-K+-ATPase expression at posttranscriptional level in rat fetal distal lung epithelial cells.
Transepithelial Na(+) transport through epithelial Na(+) channels (ENaC) on the apical membrane and Na(+)-K(+)-ATPase activity on the basolateral membrane of distal lung epithelial cells are critical for alveolar fluid clearance. Acute exposure to beta-adrenergic agonists stimulates lung fluid clearance by increasing Na(+) transport. We investigated the effects of chronic exposure to the beta(2)-adrenergic agonist terbutaline on the transepithelial Na(+) transport in rat fetal distal lung epithelia (FDLE). FDLE monolayers exposed to 10(-4) M terbutaline for 48 h had significantly increased propanolol-blockable transepithelial total and amiloride-sensitive short-circuit current (I(sc)); however, when these chronically exposed monolayers were acutely exposed to additional beta-agonists and intracellular cAMP upregulators, there was no further increase in I(sc). Monolayers exposed to terbutaline for >48 h had I(sc) similar to control cells. Ouabain-sensitive Na(+)-K(+)-ATPase activity was increased in 48-h terbutaline-exposed FDLE whose apical membranes were permeabilized with nystatin. In contrast, terbutaline did not increase amiloride-sensitive apical membrane I(sc) in FDLE whose basolateral membranes were permeabilized with nystatin. Terbutaline treatment did not affect alpha-, beta-, or gamma-ENaC mRNA or alpha-ENaC protein steady-state levels, but increased total cellular levels and rate of synthesis of alpha(1)-Na(+)-K(+)-ATPase protein in FDLE in the absence of any change in alpha(1)-Na(+)-K(+)-ATPase mRNA. Total cellular beta(1)-Na(+)-K(+)-ATPase mRNA and protein levels were not affected by terbutaline. These data suggest that FDLE have different responses from adult type II epithelial cells when chronically exposed to terbutaline, and their increased transepithelial Na(+) transport occurs via a posttranscriptional increase in alpha(1)-Na(+)-K(+)-ATPase expression.
Rahman
Muhammad S
MS
Program in Physiology and Experimental Medicine, Hospital for Sick Children Research Institute, 555 Univ. Ave., Toronto, Ontario, Canada M5G 1X8.
Gandhi
Shephali
S
Otulakowski
Gail
G
Duan
Wenming
W
Sarangapani
Aparna
A
O'Brodovich
Hugh
H
D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000584:Amiloride / Q000494:pharmacology; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism; D004847:Epithelial Cells / Q000187:drug effects / Q000201:enzymology*; D053503:Epithelial Sodium Channels / Q000235:genetics / Q000378:metabolism; D005333:Fetus / Q000166:cytology*; D005786:Gene Expression Regulation / Q000187:drug effects*; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism; D015640:Ion Channel Gating / Q000187:drug effects; D008168:Lung / Q000166:cytology*; D010042:Ouabain / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D014176:Protein Biosynthesis / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D012964:Sodium / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000235:genetics* / Q000378:metabolism; D013726:Terbutaline / Q000494:pharmacology*; D013997:Time Factors; D014158:Transcription, Genetic / Q000187:drug effects*
D000318:Adrenergic beta-Agonists; D053503:Epithelial Sodium Channels; D012333:RNA, Messenger; D010042:Ouabain; D000584:Amiloride; D012964:Sodium; D011433:Propranolol; D000242:Cyclic AMP; D000254:Sodium-Potassium-Exchanging ATPase; D013726:Terbutaline