Dmitrieva Renata I, Doris Peter A
Institute of Molecular Medicine, University of Texas, Houston, Texas 77030, USA.
Exp Biol Med (Maywood). 2002 Sep;227(8):561-9. doi: 10.1177/153537020222700803.
The highly conserved cardiotonic steroid (CS) binding site present on the ubiquitous membrane sodium pump, sodium, potassium-ATPase, appears to have been conserved by no force other than its capacity to bind CS: a family that includes plant-derived cardiac glycosides and putative endogenous vertebrate counterparts. Binding of ligand is inhibited by increased extracellular potassium. This implies functional coordination because inhibition of the sodium pump would be counterproductive when extracellular potassium is elevated. The interesting biology of the CS binding site continues to stimulate investigations into the identity of endogenous ligands, their role as pump regulators at the cellular level, and as mediators of body fluid balance and blood pressure regulation. In addition to inhibition of sodium and potassium transport, there is considerable recent evidence suggesting that the sodium pump may act as a cell signaling receptor activated by CS binding and responding by coordination of intracellular signaling pathways that can be dependent on and also independent of the reduction in transmembrane ion flux resulting directly from pump inhibition. This signaling may influence cell survival, growth, and differentiation. Recent insight into the biology of pump regulation by CS is reviewed.
普遍存在的膜钠泵（钠钾 - ATP酶）上高度保守的强心甾体（CS）结合位点，似乎除了其结合CS的能力外，没有其他力量使其得以保留：CS家族包括植物源性强心苷和假定的内源性脊椎动物对应物。细胞外钾离子浓度升高会抑制配体的结合。这意味着存在功能协调，因为当细胞外钾离子浓度升高时，抑制钠泵会产生相反的效果。CS结合位点有趣的生物学特性继续激发人们对内源性配体的身份、它们在细胞水平作为泵调节剂的作用以及作为体液平衡和血压调节介质的研究。除了抑制钠和钾的转运外，最近有大量证据表明，钠泵可能作为一种细胞信号受体，通过CS结合而激活，并通过协调细胞内信号通路做出反应，这些信号通路可能依赖于也可能独立于泵抑制直接导致的跨膜离子通量减少。这种信号传导可能影响细胞存活、生长和分化。本文综述了近期对CS调节泵生物学特性的见解。
