心房利钠肽对内皮通透性的调节是由环磷酸鸟苷介导的。

Atrial natriuretic peptide regulation of endothelial permeability is mediated by cGMP.

作者信息

Lofton C E, Newman W H, Currie M G

机构信息

Department of Cell and Molecular Pharmacology and Experimental Therapeutics, Medical University of South Carolina, Charleston 29425.

出版信息

Biochem Biophys Res Commun. 1990 Oct 30;172(2):793-9. doi: 10.1016/0006-291x(90)90744-8.

DOI:10.1016/0006-291x(90)90744-8

PMID:2173580

Abstract

Previous studies in our laboratory showed that ANP inhibits increases in endothelial monolayer permeability to macromolecules induced by thrombin. In this present study, we investigated the second messenger system involved in the influence of ANP on monolayer permeability. In bovine aortic endothelial cells (BAEC), ANP (100 nM) caused increased cGMP levels which were measurable at 30 sec and maximal at 3 min. Addition of 8-bromo cGMP (1 mM) to BAEC monolayers mimicked the actions of ANP by inhibiting thrombin- mediated increases in permeability to [125I]-labeled bovine serum albumin. Inhibition of increases in permeability by lower concentrations of ANP was enhanced by the cGMP-selective phosphodiesterase inhibitor, M&B 22948 (100 microM). The use of ANP structural analogs which stimulate cGMP production (AP III or BNP) prevented thrombin-induced increases in monolayer permeability, whereas AP-I, which does not increase cGMP levels, was ineffective.

摘要

我们实验室之前的研究表明，心钠素（ANP）可抑制凝血酶诱导的内皮细胞单层对大分子物质通透性的增加。在本研究中，我们调查了参与ANP对单层通透性影响的第二信使系统。在牛主动脉内皮细胞（BAEC）中，ANP（100 nM）可使环磷酸鸟苷（cGMP）水平升高，30秒时即可检测到，3分钟时达到最大值。向BAEC单层中添加8-溴环磷酸鸟苷（1 mM），通过抑制凝血酶介导的对[125I]标记的牛血清白蛋白通透性的增加，模拟了ANP的作用。cGMP选择性磷酸二酯酶抑制剂M&B 22948（100 microM）增强了较低浓度ANP对通透性增加的抑制作用。使用刺激cGMP产生的ANP结构类似物（AP III或脑钠肽（BNP））可防止凝血酶诱导的单层通透性增加，而不增加cGMP水平的AP-I则无效。