Identification of xanthurenic acid 8- O -β- d -glucoside and xanthurenic acid 8- O -sulfate as human natriuretic hormones
- 6 November 2007
- journal article
- editorial
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences of the United States of America
- Vol. 104 (45), 17873-17878
- https://doi.org/10.1073/pnas.0705553104
Abstract
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-beta-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.Keywords
This publication has 27 references indexed in Scilit:
- Ouabain-like factor: is this the natriuretic hormone?Current Opinion in Nephrology and Hypertension, 2000
- Two natriuretic substances in extracts of urine from normal man when salt-depleted and salt-loadedKidney International, 1976
- Enhanced end-organ responsiveness of the uremic kidney to the natriuretic factorKidney International, 1976
- On the influence of the natriuretic factor from patients with chronic uremia on the bioelectric properties and sodium transport of the isolated mammalian collecting tubule.JCI Insight, 1976
- An inhibitor of sodium transport in the urine of dogs with normal renal function.JCI Insight, 1975
- A natriuretic principle derived from kidney tissue of volume-expanded ratsJCI Insight, 1975
- The Presence of a Natriuretic Factor in Urine of Patients with Chronic Uremia. THE ABSENCE OF THE FACTOR IN NEPHROTIC UREMIC PATIENTSJCI Insight, 1974
- The Effects of the Natriuretic Factor from Uremic Urine on Sodium Transport, Water and Electrolyte Content, and Pyruvate Oxidation by the Isolated Toad BladderJCI Insight, 1974
- Inhibition of transepithelial sodium transport in the frog skin by a low molecular weight fraction of uremic serumJCI Insight, 1971
- Natriuretic Activity of a Substance Isolated from Human Urine During the Excretion of a Salt LoadNephron, 1971