Wechter W J, Murray E D
Laboratory of Chemical Endocrinology, Loma Linda University, Loma Linda, Calif., USA.
Exp Nephrol. 1998 Nov-Dec;6(6):488-90. doi: 10.1159/000020561.
This review summarizes the interesting and significant papers reported at the International Conference on Natriuretic and Digitalis-like Factors held at the ASH meeting in San Francisco, June 1-2, 1997. This area of investigation has been rejuvenated as of late with near structural determination of two ouabain-like isolates from human plasma (OLF) and bovine hypothalamus (HIF) which are apparently the same compound and the isolation and structural elucidation of a natriuretic metabolite of gamma-tocopherol. Spectroscopic information has also been obtained for two other compounds, an ouabain-like factor from bovine adrenals and HHIF from the hypothalamus. An explanation was offered for how low concentrations of digitalis-like factors can regulate vascular reactivity when the predominant isoform of the sodium pump has a low affinity for these compounds. Various groups are examining possible in vivo synthetic pathways that could lead to the production digitalis-like factors. The natriuretic metabolite of gamma-tocopherol, LLU-alpha, fits deWardener's postulates for a natriuretic hormone and is being examined for its involvement in ECF control. Once the structures for some of these ouabain-like compounds are determined and they are synthesized, these compounds will also be able to be studied employing classical pharmacologic methods.
本综述总结了1997年6月1 - 2日在旧金山举行的美国血液学会会议上召开的利钠因子和洋地黄样因子国际会议上报告的有趣且重要的论文。最近,该研究领域重新焕发生机,已近乎确定了从人血浆(OLF)和牛下丘脑(HIF)中分离出的两种哇巴因样化合物的结构,它们显然是同一化合物,还完成了γ-生育酚的一种利钠代谢产物的分离和结构解析。此外,还获得了另外两种化合物的光谱信息,一种是来自牛肾上腺的哇巴因样因子,另一种是来自下丘脑的HHIF。针对当钠泵的主要亚型对这些化合物亲和力较低时,低浓度洋地黄样因子如何调节血管反应性这一问题给出了解释。多个研究团队正在研究可能导致洋地黄样因子产生的体内合成途径。γ-生育酚的利钠代谢产物LLU-α符合德瓦德纳关于利钠激素的假设,目前正在研究其在细胞外液控制中的作用。一旦确定了其中一些哇巴因样化合物的结构并进行合成,这些化合物也将能够采用经典药理学方法进行研究。