Liu Jiang, Xie Zi-Jian
Department of Medicine, University of Toledo College of Medicine, Toledo, OH, USA.
Biochim Biophys Acta. 2010 Dec;1802(12):1237-45. doi: 10.1016/j.bbadis.2010.01.013. Epub 2010 Feb 6.
The Na/K-ATPase was discovered as an energy transducing ion pump. A major difference between the Na/K-ATPase and other P-type ATPases is its ability to bind a group of chemicals called cardiotonic steroids (CTS). The plant-derived CTS such as digoxin are valuable drugs for the management of cardiac diseases, whereas ouabain and marinobufagenin (MBG) have been identified as a new class of endogenous hormones. Recent studies have demonstrated that the endogenous CTS are important regulators of renal Na(+) excretion and blood pressure. The Na/K-ATPase is not only an ion pump, but also an important receptor that can transduce the ligand-like effect of CTS on intracellular protein kinases and Ca(2+) signaling. Significantly, these CTS-provoked signaling events are capable of reducing the surface expression of apical NHE3 (Na/H exchanger isoform 3) and basolateral Na/K-ATPase in renal proximal tubular cells. These findings suggest that endogenous CTS may play an important role in regulation of tubular Na(+) excretion under physiological conditions; conversely, a defect at either the receptor level (Na/K-ATPase) or receptor-effector coupling would reduce the ability of renal proximal tubular cells to excrete Na(+), thus culminating/resulting in salt-sensitive hypertension.
钠钾ATP酶最初被发现是一种能量转换离子泵。钠钾ATP酶与其他P型ATP酶的一个主要区别在于它能够结合一类名为强心甾类（CTS）的化学物质。植物来源的CTS，如地高辛，是治疗心脏病的重要药物，而哇巴因和海蟾蜍毒配基（MBG）已被确认为一类新的内源性激素。最近的研究表明，内源性CTS是肾脏钠排泄和血压的重要调节因子。钠钾ATP酶不仅是一种离子泵，还是一种重要的受体，能够转导CTS对细胞内蛋白激酶和钙离子信号的类配体效应。值得注意的是，这些由CTS引发的信号事件能够降低肾近端小管细胞顶端NHE3（钠氢交换体3型）和基底外侧钠钾ATP酶的表面表达。这些发现表明，内源性CTS可能在生理条件下对肾小管钠排泄的调节中发挥重要作用；相反，受体水平（钠钾ATP酶）或受体-效应器偶联的缺陷会降低肾近端小管细胞排泄钠的能力，从而导致盐敏感性高血压。
