Guerrero C, Lecuona E, Pesce L, Ridge K M, Sznajder J I
Division of Pulmonary and Critical Care Medicine, Northwestern University, Chicago, Illinois 60611, USA.
Am J Physiol Lung Cell Mol Physiol. 2001 Jul;281(1):L79-85. doi: 10.1152/ajplung.2001.281.1.L79.
Dopamine (DA) increases lung edema clearance by regulating vectorial Na+ transport and Na-K-ATPase in the pulmonary epithelium. We studied the role of the mitogen-activated protein kinase (MAPK)-extracellular signal-regulated kinase (ERK) pathway in the DA regulation of Na-K-ATPase in alveolar epithelial cells (AEC). Incubation of AEC with DA resulted in a rapid stimulation of ERK activity via dopaminergic type 2 receptors. Analysis of total RNA and protein showed a 1.5-fold increase in the Na-K-ATPase beta1-subunit mRNA levels and up to a fivefold increase in beta1-subunit protein abundance after DA stimulation, which was blocked by the MAPK kinase (MEK) inhibitors PD-98059 and U-0126. Also, the DA-ERK pathway stimulated the synthesis of a green fluorescent protein reporter gene driven by the beta1-subunit promoter, which indicates that DA regulates the Na-K-ATPase beta1-subunit at the transcriptional level. The DA-mediated increase in beta1-subunit mRNA protein resulted in an increase in functional Na pumps in the basolateral membranes of alveolar type II cells. These results suggest that the MAPK-ERK pathway is an important mechanism in the regulation of Na-K-ATPase by DA in the alveolar epithelium.
多巴胺（DA）通过调节肺上皮细胞中的向量性Na⁺转运和钠钾ATP酶来增加肺水肿清除率。我们研究了丝裂原活化蛋白激酶（MAPK）-细胞外信号调节激酶（ERK）途径在DA对肺泡上皮细胞（AEC）中钠钾ATP酶调节中的作用。用DA孵育AEC会通过多巴胺能2型受体快速刺激ERK活性。总RNA和蛋白质分析显示，DA刺激后，钠钾ATP酶β1亚基mRNA水平增加了1.5倍，β1亚基蛋白质丰度增加了多达5倍，这被MAPK激酶（MEK）抑制剂PD-98059和U-0126阻断。此外，DA-ERK途径刺激了由β1亚基启动子驱动的绿色荧光蛋白报告基因的合成，这表明DA在转录水平上调节钠钾ATP酶β1亚基。DA介导的β1亚基mRNA蛋白增加导致II型肺泡细胞基底外侧膜中功能性钠泵增加。这些结果表明，MAPK-ERK途径是DA在肺泡上皮细胞中调节钠钾ATP酶的重要机制。
