Lelievre L G, Charlemagne D, Mouas C, Swynghedauw B
Biochem Pharmacol. 1986 Oct 15;35(20):3449-55. doi: 10.1016/0006-2952(86)90611-8.
High- and low-affinity digitalis receptors coexist in rat cardiac sarcolemma. In this study, their relative involvement in the inotropic effect of ouabain was evaluated on an isolated Langendorff rat heart preparation working under isovolumic conditions at a low external calcium concentration (0.25 mM). This involvement was estimated according to both the development of the inotropic response to ouabain (10(-8)-10(-4)M) and the time course of the washing out of the biological effect. In each phenomenon considered, and whatever the index of inotropy chosen, the high-affinity digitalis receptor (EC50: 1-2 X 10(-8) M) contributed to 25-40% of the maximal inotropy (evoked by 10(-4) M ouabain). Low-affinity receptors (EC50: 1-2 X 10(-5) M) accounted for 60-75%. These apparent affinities were identical to those previously determined in sarcolemma isolated from rat heart perfused with 0.25 mM Ca2+. The biphasic effect of ouabain was related to both the inhibition of high- and low-sensitivity Na+, K+-ATPase forms and the corresponding number of ouabain-binding sites occupied. These results support the concept that the Na+, K+-ATPase highly sensitive to ouabain as revealed by lowering calcium is the in vivo manifestation of the high-sensitivity inotropic component.
高亲和力和低亲和力的洋地黄受体共存于大鼠心肌肌膜中。在本研究中，在低细胞外钙浓度（0.25 mM）的等容条件下工作的离体Langendorff大鼠心脏标本上，评估了它们对哇巴因正性肌力作用的相对参与情况。根据对哇巴因（10^(-8)-10^(-4)M）的正性肌力反应的发展以及生物效应洗脱的时间进程来估计这种参与情况。在考虑的每种现象中，无论选择何种正性肌力指标，高亲和力洋地黄受体（EC50：1-2×10^(-8) M）对最大正性肌力（由10^(-4) M哇巴因诱发）的贡献为25-40%。低亲和力受体（EC50：1-2×10^(-5) M）占60-75%。这些表观亲和力与先前在用0.25 mM Ca2+灌注的大鼠心脏分离的肌膜中测定的亲和力相同。哇巴因的双相作用与高敏感性和低敏感性Na+，K+-ATP酶形式的抑制以及相应数量的哇巴因结合位点被占据有关。这些结果支持这样的概念，即通过降低钙所揭示的对哇巴因高度敏感的Na+，K+-ATP酶是高敏感性正性肌力成分的体内表现。
