在過(guò)去的40多年中,，科學(xué)家一直相信存在一種能將體內(nèi)的鈉清除出去的天然激素,，它能制造更有效和更安全的高血壓治療方法,。目前降低鈉濃度的藥物存在嚴(yán)重的副作用,，因?yàn)樗鼈兺瑫r(shí)也會(huì)降低鉀濃度,。來(lái)自Cornell和Boyce Thompson植物研究所的科學(xué)家利用一種新技術(shù)從人尿中發(fā)現(xiàn)了一種新激素-黃尿酸衍生物-它似乎就是學(xué)者們要尋找的物質(zhì),。
結(jié)果發(fā)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發(fā)明了一種分析小分子復(fù)雜混合物的新技術(shù)，它使得確認(rèn)這種激素變得可能,。在這之前,，科學(xué)家發(fā)現(xiàn)人類(lèi)類(lèi)固醇-醛固酮能激發(fā)腎臟重吸收鈉，并分泌鉀,，這促使科學(xué)家相信應(yīng)該有一種作用相反的激素,。很多人試圖從人尿中尋找這種激素，但尿液中含有成百上千種分子,，需要的那種無(wú)法被分離,，因?yàn)樵趥鹘y(tǒng)化學(xué)分析技術(shù)中這種激素可能很容易的被分解。
大部分研究者放棄了尋找這種腎臟激素,，直到2003年一家私有公司Naturon Corp聯(lián)系了Schroeder以及來(lái)自Cornell和哈佛醫(yī)學(xué)院的研究人員,。為了完成這一任務(wù)，Schroeder發(fā)明了一種基于核磁共振光譜（NMR）的技術(shù),，傳統(tǒng)上NMR光譜只用于分析純化物質(zhì),。Schroeder的發(fā)明使得NMR能在不提純的情況下進(jìn)行分析，例如對(duì)于部分蒸餾的尿液,。結(jié)果發(fā)現(xiàn)了三種全新的物質(zhì),，其中每一種都被合成并注入老鼠體內(nèi)。然后科學(xué)家監(jiān)控老鼠的尿液,。
其中兩種物質(zhì)提高了老鼠尿液中的鈉濃度,，但保持鉀濃度恒定，這些物質(zhì)都來(lái)自常見(jiàn)代謝物尿黃酸的衍生物,。Schroeder表示,，醛固酮是一種類(lèi)固醇類(lèi)激素，而新發(fā)現(xiàn)的分子在結(jié)構(gòu)上更類(lèi)似于氨基酸衍生物,，例如神經(jīng)傳遞素多巴胺,、復(fù)合胺，因此它們可能在體內(nèi)起著其它作用,。 （教育部科技發(fā)展中心）
原文鏈接：http://www.physorg.com/news113155156.html
原始出處:
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
