Impact of β-adrenergic agonist on Na+ channel and Na+-K+-ATPase expression in alveolar type II cells

被引:83
作者
Minakata, Y
Suzuki, S
Grygorczyk, C
Dagenais, A
Berthiaume, Y
机构
[1] Ctr Hosp Univ Montreal, Ctr Rech, Montreal, PQ H2W 1T8, Canada
[2] Univ Montreal, Dept Med, Montreal, PQ H3C 3J7, Canada
关键词
adenosinetriphosphatase; epithelial sodium channel; pulmonary edema; gene expression; sodium pump; terbutaline; alveolar epithelium;
D O I
10.1152/ajplung.1998.275.2.L414
中图分类号
Q4 [生理学];
学科分类号
071003 ;
摘要
It has been shown that short-term (hours) treatment with beta-adrenergic agonists can stimulate lung liquid clearance via augmented Na+ transport across alveolar epithelial cells. This increase in Na+ transport with short-term beta-agonist treatment has been explained by activation of the Na+ channel or Na+-K(+-)ATPase by cAMP. However, because the effect of sustained stimulation (days) with beta-adrenergic agonists on the Na+ transport mechanism is unknown, we examined this question in cultured rat alveolar type II cells. Na+-K+-ATPase activity was increased in these cells by 10(-4) M terbutaline in an exposure time-dependent manner over 7 days in culture. This increased activity was also associated with an elevation in transepithelial current that was inhibited by amiloride. The enzyme's activity was also augmented by continuous treatment with dibutyryl-cAMP (DBcAMP) for 5 days. This in crease in Na+-K+-ATPase activity by 10(-4) M terbutaline was associated with an increased expression of alpha(1)-Na+-K+-ATPase mRNA and protein. beta-Adrenergic agonist treatment also enhanced the expression of the alpha-subunit of the epithelial Na+ channel (ENaC). These increases in gene expression were inhibited by propranolol. Amiloride also suppressed this long-term effect of terbutaline and DBcAMP on Na+-K+-ATPase activity. In conclusion, beta-adrenergic agonists enhance the gene expression of Na+-K+-ATPase, which results in an increased quantity and activity of the enzyme. This heightened expression is also associated with augmented ENaC expression. Although the cAMP system is involved, the inhibition of enhanced enzyme activity with amiloride suggests that increased Na+ entry at the apical surface plays a role in this process.
引用
收藏
页码:L414 / L422
页数:9
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