| Title | Long term terbutaline exposure stimulates {alpha}1-Na+-K+-ATPase expression at posttranscriptional level in rat fetal distal lung epithelial cells. | | Author(s) | Rahman MS, Gandhi SG, Otulakowski G, Duan W, Sarangapani A, O'Brodovich HM | | Institution | University of Manitoba. | | Source | Am J Physiol Lung Cell Mol Physiol 2009 Oct 30. | | Abstract | 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 is 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 beta2-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 (Isc); however, when these chronically exposed monolayers were acutely exposed to additional beta-agonists and intracellular cAMP-upregulators, there was no further increase in Isc. Monolayers exposed to terbutaline for > 48 h had Isc 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 Isc 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 alpha1- Na(+)-K(+)-ATPase protein in FDLE in the absence of any change in alpha1- Na(+)-K(+)-ATPase mRNA. Total cellular beta1-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 post-transcriptional increase in alpha1-Na(+)-K(+)-ATPase expression. Key words: epithelial sodium channel, ENaC, sodium pump, ion transport. | | Language | ENG | | Pub Type(s) | JOURNAL ARTICLE
| | PubMed ID | 19880505 |
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