HIGH-AFFINITY OUABAIN BINDING-SITE AND LOW-DOSE POSITIVE INOTROPIC EFFECT IN RAT MYOCARDIUM
HIGH-AFFINITY OUABAIN BINDING-SITE AND LOW-DOSE POSITIVE INOTROPIC EFFECT IN RAT MYOCARDIUM
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DOI：
10.1038/296167a0
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发表时间：
1982-01-01
期刊：
影响因子：
64.8
通讯作者：
GATHIRAM, P
中科院分区：
文献类型：
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作者：
ADAMS, RJ;SCHWARTZ, A;GATHIRAM, P
洋地黄苷正性肌力作用的机制尚不清楚。一种理论认为洋地黄与（Na ++ K+）ATP酶（钠泵）的结合和随后的抑制与心肌收缩力增加之间存在因果关系1 - 6。通过这种机制，收缩力的增加将继发于细胞内钠浓度的升高，然后通过钠-钙交换机制引起细胞内钙浓度的增加4 - 6。另一种理论认为，洋地黄与（Na ++ K+）ATP酶的结合导致肌膜钙池增加6 - 9，表明变力作用可能是由于洋地黄-（Na ++ K+）ATP酶受体复合物的形成与心肌钙可用性和利用率增加之间的因果关系，不包括钠泵的抑制7 - 9。我们现在报告，两个不同的正性肌力位点哇巴因存在于大鼠心室肌条。高亲和力反应（ED 50 = 0.5 µ M）与一个明显的高亲和力位点相关，该位点可通过3H-哇巴因与完整大鼠心室肌细胞的结合检测到。这些高亲和力位点与抑制大鼠心室肌膜制备物（Na ++ K+）ATP酶活性所需的哇巴因浓度（IC 50）无关，表明在大鼠心室中哇巴因强心作用的高亲和力位点可能与抑制（Na ++ K+）ATP酶无关。然而，低亲和力位点与该酶的抑制有关。
The mechanism of the positive inotropic effect of digitalis glycosides remains unclear. One theory suggests a causal relationship between the binding to and consequent inhibition of (Na++K+) ATPase (the sodium pump) by digitalis and an increased myocardial contractile force1–6. By this mechanism, the increased force of contraction would occur secondary to an elevation of intracellular sodium concentration which then causes an increased intracellular concentration of calcium via a sodium–calcium exchange mechanism4–6. Another theory proposes that the binding of digitalis to (Na++K+) ATPase causes an increase in a sarcolemmal calcium pool6–9, suggesting that the inotropic effect could be due to a causal relationship between the formation of the digitalis–(Na++K+)ATPase receptor complex and increased myocardial calcium availability and utilization, exclusive of an inhibition of the sodium pump7–9. We now report that two distinct positive inotropic sites for ouabain exist in rat ventricular strips. The higher-affinity response (ED50= 0.5 µM) correlates with an apparent high-affinity site which can be detected by3H-ouabain binding to intact rat ventricular myocytes. These higher-affinity sites do not correlate with concentrations (IC50) of ouabain necessary to inhibit (Na++K+)ATPase activity of sarcolemma preparations prepared from rat ventricles, suggesting that in the rat ventricle the high-affinity site for the inotropic effect of ouabain may not be related to inhibition of (Na++K+)ATPase. The low-affinity site is, however, related to inhibition of this enzyme.