Godfraind T, Ghysel-Burton J, De Pover A
Nature. 1982 Oct 28;299(5886):824-6. doi: 10.1038/299824a0.
The Na+, K+-pump controls a wide variety of cellular systems and its inhibition by cardiac glycosides modifies important physiological functions and evokes several pharmacological effects (refs 1, 2 and refs therein). However, not all the actions of cardiac glycosides can be attributed to Na+, K+-pump inhibition and several observations show that, at low doses, cardiac glycosides stimulate the pump. It has been proposed that their positive inotropic effect could be the sum of two processes: the inhibition of the pump and a still unknown additional inotropic mechanism. In guinea pig heart, low doses of ouabain interact with high-affinity binding sites, which differ from the lower-affinity sites responsible for Na+, K+-pump inhibition. It has been suggested that ouabain interaction with these high-affinity sites could be responsible for the additional inotropic mechanism. The existence of two classes of ouabain-binding sites has been documented not only in guinea pig heart, but also in dog, rat and human heart. Dihydroouabain, a derivative of ouabain in which the lactone ring is saturated, is about 50-fold less potent than ouabain as an inhibitor of Na+, K+-pump and does not stimulate the pump at low doses. Its inotropic effect can be entirely accounted for by the inhibition of the pump. We have examined the pharmacological action of ouabain in the presence of dihydroouabain and report here that dihydroouabain reduces ouabain inotropic action but not Na+, K+-pump inhibition.
钠钾泵控制着多种细胞系统，强心苷对其的抑制作用会改变重要的生理功能并引发多种药理效应（参考文献1、2及其中的参考文献）。然而，强心苷的所有作用并非都可归因于对钠钾泵的抑制，多项观察表明，在低剂量时，强心苷会刺激该泵。有人提出，它们的正性肌力作用可能是两个过程的总和：泵的抑制作用以及一种尚不明确的额外的正性肌力机制。在豚鼠心脏中，低剂量的哇巴因会与高亲和力结合位点相互作用，这些位点不同于负责抑制钠钾泵的低亲和力位点。有人认为，哇巴因与这些高亲和力位点的相互作用可能是额外正性肌力机制的原因。不仅在豚鼠心脏中，而且在狗、大鼠和人类心脏中都已证实存在两类哇巴因结合位点。双氢哇巴因是哇巴因的一种衍生物，其中内酯环饱和，作为钠钾泵抑制剂，其效力比哇巴因低约50倍，并且在低剂量时不会刺激该泵。其正性肌力作用完全可由对泵的抑制作用来解释。我们研究了在双氢哇巴因存在的情况下哇巴因的药理作用，并在此报告双氢哇巴因会降低哇巴因的正性肌力作用，但不会降低对钠钾泵的抑制作用。
