儿茶酚胺参与哇巴因心脏作用的证据：正性变时效应。
Evidence for participation of catecholamines in cardiac action of ouabain: positive chronotropic effect.
作者信息
Seifen E
出版信息
Br J Pharmacol. 1974 Aug;51(4):481-90. doi: 10.1111/j.1476-5381.1974.tb09665.x.
1 The shortening of cycle length (=positive chronotropic effect) by ouabain produced in isolated spontaneously beating atria of the guinea-pig was analyzed.2 The action of ouabain was dose-dependent; threshold response was seen at 1 x 10(-7) M, and maximal response occurred at 4 x 10(-7) M. The half-time of the ouabain effect was about 20 minutes.3 The positive chronotropic effect of ouabain was reduced to 40% by beta-adrenoceptor blockade (3.3 x 10(-9) M propranolol) or by reserpine-depletion of catecholamines. Incubation of reserpine-treated atria with noradrenaline partially restored the action of ouabain.4 The effect of ouabain was greatly dependent upon the calcium concentration. The optimal calcium level was 2.5 x 10(-3) M. Calcium and ouabain acted synergistically.5 Increasing calcium concentrations inhibited the positive chronotropic effect of noradrenaline in a manner similar to increasing ouabain concentrations.6 A hypothesis is proposed which explains the chronotropic effect of ouabain on the basis of two mechanisms: (1) increase of the catecholamine concentration affecting the pacemaker; (2) mobilization of calcium, i.e. increase of the biologically effective intracellular calcium level.
1 分析了哇巴因对豚鼠离体自发搏动心房产生的周期长度缩短（即正性变时作用）。
2 哇巴因的作用呈剂量依赖性；在1×10⁻⁷ M时可见阈反应，最大反应出现在4×10⁻⁷ M时。哇巴因作用的半衰期约为20分钟。
3 β-肾上腺素能受体阻断（3.3×10⁻⁹ M普萘洛尔）或利血平耗竭儿茶酚胺后，哇巴因的正性变时作用降低至40%。用去甲肾上腺素孵育经利血平处理的心房可部分恢复哇巴因的作用。
4 哇巴因的作用很大程度上取决于钙浓度。最佳钙水平为2.5×10⁻³ M。钙和哇巴因起协同作用。
5 增加钙浓度以类似于增加哇巴因浓度的方式抑制去甲肾上腺素的正性变时作用。
6 提出了一种假说，该假说基于两种机制解释哇巴因的变时作用：（1）影响起搏点的儿茶酚胺浓度增加；（2）钙的动员，即生物有效细胞内钙水平增加。
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