CHARACTERIZATION OF HUMAN ENDOGENOUS DIGOXIN-LIKE FACTOR

几个实验室的数据显示， 内源性地高辛样免疫反应因子（DLIF） 原发性高血压（EH）患者血清和 妊娠高血压综合征（PIH） 我们有 证明肾上腺分泌DLIF。 证据 也表明这些因素是内源性抑制剂， 哇巴因敏感的钠-钾ATP酶。 钠钾 ATP酶是血管平滑肌收缩的调节剂， 微动脉松弛。 这种ATP酶的抑制增强了 血管平滑肌收缩引起血管收缩 导致全身性高血压 鉴于这些考虑 DLIF可能是导致 在这些形式的高血压中观察到的血管收缩效应 因此在这些目前未知的病因学中起作用 疾病 我们提出一个工作假设：DLIF是内源性抑制剂 哇巴因敏感的钠-钾ATP酶， 高血压病和妊高征患者血压升高的机制。 在这 我们将测试这个工作假设的第一部分。 证明来自人肾上腺的DLIF是一种 ATP酶抑制剂需要纯化和生物 这是一种内生性因素。 本项目的目的是分离、纯化和表征 从以下来源获得的DLIF的化学性质和生物活性 人体肾上腺 表征将使用 四个独立的分析系统：放射免疫分析，哇巴因- 从ATP酶置换，抑制钠-钾 ATP酶和抑制红细胞中的铷摄取。 到 为DLIF提供更特异性的免疫测定， 这个因素将得到发展。 因为DLIF与 血清蛋白可调节其生物活性， 这种内源性因子对血清蛋白的特性将 也被研究。 这项研究将提供物理-生化和生物 DLIF的表征并检验DLIF是 钠-钾ATP酶的内源性抑制剂。 总 提出内源性地高辛样 免疫活性、内源性ATP酶抑制剂和EH或PIH可 然后在未来的研究中加以解决。 这些内源性化合物 可以证明有助于阐明的机制和/或提供 这些疾病的标志物。

Data from several laboratories have demonstrated elevated levels of endogenous digoxin-like immunoreactive factors (DLIF) in serum from patients with essential hypertension (EH) and from women with pregnancy induced hypertension (PIH). We have demonstrated that the adrenal gland secretes DLIF. Evidence also suggests that these factors are endogenous inhibitors of ouabain-sensitive sodium-potassium ATPase. Sodium-potassium ATPase is a modulator of vascular smooth muscle contraction and relaxation in arterioles. Inhibition of this ATPase enhances vascular smooth muscle contraction causing vasoconstriction which leads to systemic hypertension. Given these considerations it seems plausible that DLIF might be responsible for the vasoconstric- tion effects observed in these forms of hypertension and hence play a role in the presently unknown etiology of these diseases. We propose a working hypothesis: DLIF are endogenous inhibitors of ouabain-sensitive sodium-potassium ATPase and by this mechanism they increase blood pressure in EH and PIH. In this project we will test the first part of this working hypothesis. Demonstrating that DLIF from human adrenal glands is an inhibitor of ATPase requires purification and biological characterization of this endogenous factor. The aim of this project is to isolate, purify, and characterize the chemical nature and the biological activity of DLIF obtained from human adrenal glands. Characterization will be done utilizing four independent assays systems: radioimmunoassay, ouabain- displacement from ATPase, inhibition of sodium-potassium ATPase, and inhibition of rubidium-uptake in erythrocytes. To provide a more specific immunoassay for DLIF, antibodies against this factor will be developed. Because the binding of DLIF to serum proteins may regulate its bioactivity, the binding characteristics of this endogenous factor to serum proteins will also be studied. This research will provide the physical-biochemical and biological characterization of DLIF and test the hypothesis that DLIF are endogenous inhibitors of sodium-potassium ATPase. The general hypothesis proposing a link between endogenous digoxin-like immunoactivity, endogenous ATPase inhibitors, and EH or PIH can then be addressed in future studies. These endogenous compounds may prove useful in elucidating the mechanism of and/or provide a marker for these diseases.