两种内源性钠钾ATP酶抑制剂，海蟾蜍精和哇巴因，对离体大鼠主动脉的作用。

Effects of two endogenous Na+,K(+)-ATPase inhibitors, marinobufagenin and ouabain, on isolated rat aorta.

作者信息

Bagrov A Y, Roukoyatkina N I, Pinaev A G, Dmitrieva R I, Fedorova O V

机构信息

Laboratory of Behavioral Sciences, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA.

出版信息

Eur J Pharmacol. 1995 Feb 14;274(1-3):151-8. doi: 10.1016/0014-2999(94)00735-p.

DOI:10.1016/0014-2999(94)00735-p

PMID:7768267

Abstract

Previously, we reported that the venom of Bufo marinus toad contains a Na+,K(+)-ATPase inhibitor with potent vasoconstrictor activity. In the present study, using thin-layer chromatography in Silicagel 60 F254 + 366, we separated a vasoactive substance from a mixture of steroids from Bufo marinus venom. Based on chromatographic mobility of this substance and typical color reaction after its vizualization with SbCl3, we identified it as a previously described steroid, marinobufagenin. Vasoconstrictor and Na+,K+ pump inhibitory properties of marinobufagenin were studied in isolated rat aortic rings and compared with those of ouabain. Ouabain (10-100 mumol.1-1) produced weak vasoconstriction, which was blocked by 2 mumol.1-1 phentolamine. 10 mumol.1-1 ouabain stimulated, and at higher concentrations inhibited, the Na+,K+ pump. 2 mumol.1-1 phentolamine abolished the activating effect of 10 mumol.1-1 ouabain on the Na+,K+ pump, but did not alter the inhibitory action of higher concentrations of ouabain. By contrast, marunibufagenin elicited rapid and strong vasoconstriction and inhibited ouabain-sensitive 86Rb uptake. Antidigoxin antibody antagonized the vasoconstrictor responses to marinobufagenin, but not to ouabain. 2 mumol.1-1 phentolamine did not alter the constrictor effect of marinobufagenin. In solid-phase digoxin immunoassay, marinobufagenin demonstrated higher digoxin-like immunoreactivity than ouabain.

摘要

此前，我们报道过，海蟾蜍毒液中含有一种具有强大血管收缩活性的Na⁺,K⁺-ATP酶抑制剂。在本研究中，我们使用硅胶60 F254 + 366薄层层析法，从海蟾蜍毒液的类固醇混合物中分离出一种血管活性物质。根据该物质的色谱迁移率以及用SbCl₃显色后的典型颜色反应，我们将其鉴定为一种先前描述过的类固醇，海蟾蜍精。我们在离体大鼠主动脉环中研究了海蟾蜍精的血管收缩和Na⁺,K⁺泵抑制特性，并与哇巴因进行了比较。哇巴因（10 - 100 μmol·L⁻¹）产生微弱的血管收缩作用，可被2 μmol·L⁻¹酚妥拉明阻断。10 μmol·L⁻¹哇巴因刺激Na⁺,K⁺泵，而在更高浓度时则抑制该泵。2 μmol·L⁻¹酚妥拉明消除了10 μmol·L⁻¹哇巴因对Na⁺,K⁺泵的激活作用，但未改变更高浓度哇巴因的抑制作用。相比之下，海蟾蜍精引起快速且强烈的血管收缩，并抑制哇巴因敏感的⁸⁶Rb摄取。抗地高辛抗体可拮抗海蟾蜍精的血管收缩反应，但不能拮抗哇巴因的反应。2 μmol·L⁻¹酚妥拉明未改变海蟾蜍精的收缩作用。在固相地高辛免疫测定中，海蟾蜍精显示出比哇巴因更高的心苷样免疫反应性。