在过去的40多年中，科学家一直相信存在一种能将体内的钠清除出去的天然激素，它能制造更有效和更安全的高血压治疗方法。目前降低钠浓度的药物存在严重的副作用，因为它们同时也会降低钾浓度。来自Cornell和Boyce Thompson植物研究所的科学家利用一种新技术从人尿中发现了一种新激素-黄尿酸衍生物-它似乎就是学者们要寻找的物质。
结果发表在最近一期Proceedings of the National Academy of Sciences上，文章合作者，BTI助理教授Frank Schroeder发明了一种分析小分子复杂混合物的新技术，它使得确认这种激素变得可能。在这之前，科学家发现人类类固醇-醛固酮能激发肾脏重吸收钠，并分泌钾，这促使科学家相信应该有一种作用相反的激素。很多人试图从人尿中寻找这种激素，但尿液中含有成百上千种分子，需要的那种无法被分离，因为在传统化学分析技术中这种激素可能很容易的被分解。
大部分研究者放弃了寻找这种肾脏激素，直到2003年一家私有公司Naturon Corp联系了Schroeder以及来自Cornell和哈佛医学院的研究人员。为了完成这一任务，Schroeder发明了一种基于核磁共振光谱（NMR）的技术，传统上NMR光谱只用于分析纯化物质。Schroeder的发明使得NMR能在不提纯的情况下进行分析，例如对于部分蒸馏的尿液。结果发现了三种全新的物质，其中每一种都被合成并注入老鼠体内。然后科学家监控老鼠的尿液。
其中两种物质提高了老鼠尿液中的钠浓度，但保持钾浓度恒定，这些物质都来自常见代谢物尿黄酸的衍生物。Schroeder表示，醛固酮是一种类固醇类激素，而新发现的分子在结构上更类似于氨基酸衍生物，例如神经传递素多巴胺、复合胺，因此它们可能在体内起着其它作用。 （教育部科技发展中心）
原文链接：http://www.physorg.com/news113155156.html
原始出处:
Published online before print October 31, 2007, 10.1073/pnas.0705553104
PNAS | November 6, 2007 | vol. 104 | no. 45 | 17873-17878
Identification of xanthurenic acid 8-O--D-glucoside and xanthurenic acid 8-O-sulfate as human natriuretic hormones
Christopher D. Cain*,, Frank C. Schroeder,, Stewart W. Shankel*, Mark Mitchnick*, Michael Schmertzler*, and Neal S. Bricker*
*Naturon Pharmaceutical Corporation, New Canaan, CT 06840; and Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, 240 Longwood Avenue, Boston, MA 02115
Edited by Jerrold Meinwald, Cornell University, Ithaca, NY, and approved September 17, 2007 (received for review June 13, 2007)
Hormonal regulation of salt excretion and water balance by the kidneys is well documented. Before 1961, it was widely believed that the glomerular filtration rate and the steroid hormone aldosterone controlled sodium balance in the body. In 1961, deWardener et al. [de Wardener HE, Mills IH, Clapham WF, Hayter CJ (1961) Clin Sci 21:249–258] showed that when these two variables were controlled, the kidney was still able to increase sodium excretion in response to a salt load. Several lines of evidence argued for a small-molecule signal as a definitive modulator of sodium excretion by the kidney. However, the chemical nature of the suspected natriuretic agent remained unknown. Here we report the identification and natriuretic activity of two closely related small molecules isolated from human urine, xanthurenic acid 8-O--D-glucoside and xanthurenic acid 8-O-sulfate. The two compounds were partially purified by activity-guided fractionation and subsequently identified by using NMR spectroscopic analyses of enriched active fractions. Both compounds caused substantial and sustained (1- to 2-h) natriuresis in rats and no or minimal concomitant potassium excretion. We believe these compounds constitute a class of kidney hormones that also could influence sodium transport in nonkidney tissues given that these tryptophan metabolites presumably represent evolutionarily old structures.
diuresis | kidney | nonpeptidic | sodium homeostasis | NMR spectroscopy
