Minakata Y, Suzuki S, Grygorczyk C, Dagenais A, Berthiaume Y
Centre de Recherche, Centre Hospitalier de l'Université de Montréal, Montreal, Quebec H2W 1T8, Canada.
Am J Physiol. 1998 Aug;275(2):L414-22. doi: 10.1152/ajplung.1998.275.2.L414.
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 increase in Na+-K+-ATPase activity by 10(-4) M terbutaline was associated with an increased expression of alpha1-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.
研究表明，用β-肾上腺素能激动剂进行短期（数小时）治疗可通过增强Na⁺跨肺泡上皮细胞的转运来刺激肺液清除。短期β-激动剂治疗使Na⁺转运增加已被解释为cAMP激活了Na⁺通道或Na⁺-K⁺-ATP酶。然而，由于β-肾上腺素能激动剂持续刺激（数天）对Na⁺转运机制的影响尚不清楚，我们在培养的大鼠II型肺泡细胞中研究了这个问题。在培养7天的过程中，10⁻⁴M特布他林以暴露时间依赖的方式增加了这些细胞中的Na⁺-K⁺-ATP酶活性。这种活性增加还与氨氯地平抑制的跨上皮电流升高有关。用二丁酰-cAMP（DBcAMP）连续处理5天也增强了该酶的活性。10⁻⁴M特布他林使Na⁺-K⁺-ATP酶活性增加与α1-Na⁺-K⁺-ATP酶mRNA和蛋白质表达增加有关。β-肾上腺素能激动剂治疗还增强了上皮Na⁺通道（ENaC）α亚基的表达。这些基因表达的增加被普萘洛尔抑制。氨氯地平也抑制了特布他林和DBcAMP对Na⁺-K⁺-ATP酶活性的这种长期影响。总之，β-肾上腺素能激动剂增强了Na⁺-K⁺-ATP酶的基因表达，导致该酶的数量和活性增加。这种增强的表达还与ENaC表达增加有关。虽然cAMP系统参与其中，但氨氯地平对增强的酶活性的抑制表明，顶端表面Na⁺进入增加在这个过程中起作用。
