PHYSIOLOGIC ROLE OF ENDOGENOUS DIGITALIS-LIKE FACTOR

人体肾上腺合成并分泌多种重要的 调节激素 我们已经证明肾上腺皮质是一种 富含内源性地高辛样免疫反应因子（DLIF）， 分泌DLIF进入循环。 我们还纯化了DLIF， 均匀性，确定其分子量和化学组成。 的 内源性DLIF的化学组成与 强心作用的强心甾内酯。 多项研究表明， 原发性肝癌患者血清中内源性DLIF水平 高血压（EH），妊娠高血压（PIH），以及 心血管功能障碍 DLIF可调节 哇巴因敏感的钠-钾ATP酶。 Na/K-ATP酶（钠泵）是一种 是小动脉中血管平滑肌张力重要调节剂， 其他心血管事件。 抑制钠泵导致 导致全身性高血压的血管收缩。 因此，DLIF 肾上腺皮质分泌的高密度脂蛋白可能在EH和妊高征的发病中起一定作用。 我们提出了一个工作假设：人肾上腺皮质的DLIF是 哇巴因敏感性钠-钾ATP酶的内源性抑制剂 这一机制会影响哺乳动物的血压。 该项目的目的是确定详细的分子结构， DLIF并表征从以下获得的该因子的生物活性： 肾上腺组织 将使用四个独立的 洋地黄样活性的测定;免疫反应性，受体结合， 钠-钾ATP酶活性和钠泵活性。 这项研究将提供急需的生化鉴定， 来自肾上腺皮质的DLIF，将这些因子与来自血浆的DLIF进行比较， 检验肾上腺DLIF是内源性抑制剂的假设， 钠-钾ATP酶。 这些因素可能有助于阐明 负责EH或PIH的机制，并提供急需的诊断 这些疾病的标志物。

The human adrenal synthesizes and secretes a variety of important regulatory hormones. We have shown that the adrenal cortex is a tissue rich in endogenous digoxin-like immunoreactive factor (DLIF) and that is secretes DLIF into the circulation. We have also purified DLIF to homogeneity, determined its molecular weight and chemical composition. The chemical composition of endogenous DLIF is remarkably similar to that of the cardioactive cardenolides. Several studies have demonstrated elevated levels of endogenous DLIF in serum from patients with essential hypertension (EH), pregnancy induced hypertension (PIH), and during cardiovascular dysfunction. DLIF may regulate the enzymatic activity of ouabain-sensitive sodium-potassium ATPase. Na/K-ATPase (sodium pump) is an important modulator of vascular smooth muscle tone in arterioles as well as other cardiovascular events. Inhibition of the sodium pump causes vasoconstriction which leads to systemic hypertension. Therefore, DLIF from the adrenal cortex may play a role in the etiology of EH and PIH. We propose a working hypothesis: DLIF from human adrenal cortex are endogenous inhibitors of ouabain-sensitive sodium-potassium ATPase and by this mechanism they affect blood pressure in mammals. The aim of this project is to define the detailed molecular structure of DLIF and characterize the biological activity of this factor obtained from adrenal tissues. Characterization will be done using four independent assays of digitalis-like activity; immunoreactivity, receptor binding, sodium-potassium ATPase enzymatic activity, and sodium pump activity. This research will provide the much needed biochemical identification of DLIF from adrenal cortex, compare these factors to DLIF from plasma, and test the hypothesis that DLIF from adrenals are endogenous inhibitors of sodium-potassium ATPase. These factors may prove useful in elucidating the mechanism responsible for EH or PIH and provide much needed diagnostic markers for these diseases.