Lopatina Ekaterina V, Kipenko Anna V, Pasatetskaya Natalia A, Penniyaynen Valentina A, Krylov Boris V
a Department of the Experimental Physiology and Pharmacology Federal Almazov North-West Medical Research Centre, 2 Akkuratova St., 197341 St. Petersburg, Russia.
b Laboratory of the Excitable Membrane Pavlov Institute of Physiology of Russian Academy of Sciences, 6 Makarova Emb., 199034 St. Petersburg, Russia.
Can J Physiol Pharmacol. 2016 Oct;94(10):1110-1116. doi: 10.1139/cjpp-2015-0577. Epub 2016 Aug 24.
Endogenous digitalis-like factors were found in the mammalian and human blood. It was the starting point for the elucidation of the new non-pumping function of the Na,K-ATPase. It was previously well known that Na,K-ATPase is a pharmacological target receptor for cardiac glycosides (J.C. Skou. 1957. Biochim. Biophys. Acta, 23: 394-401). We have investigated the trophotropic effects of such agents as ouabain, epinephrine, norepinephrine, atenolol, and comenic acid using the organotypic tissue culture combined with the reconstruction of optical cross sections and confocal microscopy. It was shown that the growth zone of organotypic culture forms a multidimensional structure. Our results indicate that the cardiac glycoside ouabain applied in endogenous concentrations (10, 10 mol/L) can modulate transducer function of Na,K-ATPase and control the cell growth and proliferation. It was also shown that Src-kinase is involved in "endogenous" ouabain activated intracellular pathways as a series unit. Epinephrine (10-10 mol/L) and comenic acid (10-10 mol/L) were demonstrated to modulate the growth of 10- to 12-day-old chicken embryo cardiac tissue explants in a dose-dependent manner. Epinephrine and comenic acid regulate growth and proliferation of the cardiac tissue via receptor-mediated modulation Na,K-ATPase as a signal transducer. The trophotropic effects of the investigated agents specifically control the heart remodeling phenomenon.
在哺乳动物和人类血液中发现了内源性类洋地黄因子。这是阐明钠钾ATP酶新的非泵功能的起点。此前人们已经熟知钠钾ATP酶是强心苷的药理学靶标受体（J.C. 斯科，1957年。《生物化学与生物物理学报》，23: 394 - 401）。我们使用器官型组织培养结合光学横截面重建和共聚焦显微镜，研究了哇巴因、肾上腺素、去甲肾上腺素、阿替洛尔和科美酸等药物的营养性作用。结果表明，器官型培养的生长区形成了多维结构。我们的结果表明，以内源性浓度（10⁻¹⁰、10⁻⁹摩尔/升）应用的强心苷哇巴因可以调节钠钾ATP酶的转导功能，并控制细胞生长和增殖。还表明，Src激酶作为串联单元参与了“内源性”哇巴因激活的细胞内信号通路。已证明肾上腺素（10⁻¹⁰ - 10⁻⁹摩尔/升）和科美酸（10⁻¹⁰ - 10⁻⁹摩尔/升）以剂量依赖方式调节10至12日龄鸡胚心脏组织外植体的生长。肾上腺素和科美酸通过受体介导的对作为信号转导器的钠钾ATP酶的调节来调控心脏组织的生长和增殖。所研究药物的营养性作用特异性地控制心脏重塑现象。
