Identification of xanthurenic acid 8-
            <i>O</i>
            -β-
            <scp>d</scp>
            -glucoside and xanthurenic acid 8-
            <i>O</i>
            -sulfate as human natriuretic hormones

Cain, Christopher D.; Schroeder, Frank C.; Shankel, Stewart W.; Mitchnick, Mark; Schmertzler, Michael; Bricker, Neal S.

doi:10.1073/pnas.0705553104

Cited by 23 publications

(34 citation statements)

References 25 publications

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“…3A). However, the addition of xanthministered xanthurenic acid intravenously as a bolus injection and an infusion to rats, because a detailed method is not described in the report by Cain et al (1). As a result, we observed the diuresis by the xanthurenic acid infusion.…”

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confidence: 47%

“…Cain et al failed to obtain the diuresis by the xanthurenic acid administration in rats (1), and this is the first report showing the diuresis in rats administered with xanthurenic acid. They did not describe the dosage in the report (1), and their dosage might be lower than our dosage. In addition, their infusion was via the artery, but our administration was from the vein.…”

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confidence: 99%

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Diuresis by intravenous administration of xanthurenic acid in rats, and inhibition by probenecid

et al. 2014

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The conjugates with sulfate and glucoside of xanthurenic acid, a tryptophan metabolite, were reported to show natriuresis. Sulfotransferase for xanthurenic acid works in the renal proximal tubule to produce the sulfate of xanthurenic acid as well as the liver, and we recently found that xanthurenic acid is a substrate of renal organic anion transporter OAT1. The purpose of this study was to examine relationship between the transport by OAT1 and diuresis related with xanthurenic acid. Drug transport experiment using Xenopus laevis oocytes represented that probenecid inhibited xanthurenic acid uptake by rat OAT1 (rOAT1). Although no diuresis was recognized by the intravenous injection of xanthurenic acid as a bolus in rats, the addition of its infusion exhibited natriuresis. Simultaneous administration of probenecid significantly decreased the urine volume and excreted amounts of sodium into urine. These findings showed the diuresis by the xanthurenic acid administration, and it was probenecid-sensitive. The rOAT1-mediated transport of xanthurenic acid might, at least in part, contribute to its diuretic effect.In the renal proximal tubules, organic anion transporters secrete endogenous metabolites, drugs, and xenobiotics into urine. From the mid-1990s, cDNA of renal organic anion transporters has been isolated, and its function and expression have been characterized. Organic anion transporters OAT1 and OAT3 are thought to be responsible for the renal tubular uptake of organic anions from blood, and multidrug resistance-associated protein MRP4 is the strong candidate mediating their efflux into lumen (2). Our laboratory has been interested in transport of bioactive substances by OAT1 and OAT3. Recently, we examined interaction of the metabolites of the kynurenine pathway, a main route for the tryptophan metabolism, with OAT1 and OAT3, and represented that kynurenic acid and xanthurenic acid were transported by them (5, 6). Kynurenic acid antagonizes N-methyl D-aspartate (NMDA) receptor in the brain under physiological conditions, and is accepted as the key molecule in several psychiatric disorders (3). Xanthurenic acid is closely structurally related to kynurenic acid (Fig.

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confidence: 99%

Diuresis by intravenous administration of xanthurenic acid in rats, and inhibition by probenecid

et al. 2014

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“…In fact, 4-hydroxyl moiety of XA molecule is in a para-position to the nitrogen atom and has weak phenolic properties, suggesting that it seems unlikely to be sulfated. The nuclear magnetic resonance spectroscopic analyses of XA sulfate that was recently purified from urine also clearly demonstrated the sulfoconjugation occurred at 8-hydroxyl position (Cain et al, 2007). at ASPET Journals on May 11, 2018 jpet.aspetjournals.org…”

Section: Discussionmentioning

confidence: 96%

Involvement of ST1B Subfamily of Cytosolic Sulfotransferase in Kynurenine Metabolism to Form Natriuretic Xanthurenic Acid Sulfate

Senggunprai¹,

Yoshinari²,

Shimada³

et al. 2008

The Journal of Pharmacology and Experimental Therapeutics

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Natriuretic substances are a group of molecules affecting sodium homeostasis in the body. Recently, two new molecules having natriuresis effects, xanthurenic acid 8-O-␤-D-glucoside and xanthurenic acid 8-O-sulfate (XA sulfate), have been isolated from human urine. In the present study, we have investigated the sulfation of xanthurenic acid (XA) in mouse tissues to assess the contribution of specific sulfotransferases (STs) to the reaction. Cytosols from tissues of both sexes of C57BL/6N mice (liver, stomach, jejunum, colon, and kidney) were capable of forming XA sulfate, with various K m values. Jejunum cytosol showed the lowest K m value, and its V max /K m value was much greater than those of other tissues. The kinetic analyses with recombinant mouse (m) STs (Sult1a1, Sult1b1, Sult1c2, and Sult1d1) showed the lowest K m value for mSult1b1, and the value was comparable with that for jejunum cytosol. The highest expression of mSult1b1 in small intestine was confirmed at the mRNA and protein levels. mSult1b1 is thus suggested as a major enzyme responsible for XA sulfation in jejunum. Similar to mSult1b1, human SULT1B1 and rat Sult1b1 mediated XA sulfation efficiently. Thus, XA is likely to be an endogenous substrate for ST1B members. In contrast to XA, an XA-related compound, kynurenic acid strongly inhibited mSult1b1-mediated sulfations, with IC 50 values at a micromolar range. These results indicate the functional role of ST1B subfamily of ST in XA sulfate formation in the body.

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“…4,5) Cain et al reported that 8-O--D-glucoside and 8-O-sulfate of xanthurenic acid caused natriuresis in rats. 28) Sulfation of xanthurenic acid occurred in various tissues including the liver, stomach, jejunum, colon, and kidney, and sulfotransferase SULT1C2 was exhibited to be predominantly expressed in the proximal tubule, where OAT1 and OAT3 work. 29,30) Accordingly, it is intriguing whether the formation of xanthurenic acid sulfate followed by its tubular uptake by OAT1 and OAT3 is responsible for diuresis.…”

Section: Discussionmentioning

confidence: 99%

Transport of Xanthurenic Acid by Rat/Human Organic Anion Transporters OAT1 and OAT3

Uwai

Honjo

2013

Bioscience, Biotechnology, and Biochemistry

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Kynurenic acid, a tryptophan metabolite, is involved in psychiatric disease. Our laboratory previously described its transport by rat/human organic anion transporters rOAT1, hOAT1, rOAT3 and hOAT3, which are involved in drug disposition. In this study, we performed an uptake experiment using Xenopus laevis oocytes to examine the transport of xanthurenic acid, a tryptophan catabolite and kynurenic acid analog, by various transporters. All the transporters tested stimulated the uptake of xanthurenic acid into oocytes. The transport activity of xanthurenic acid by hOAT1 was greater than that by rOAT1. In OAT3, the rat homolog showed efficient transport, compared with hOAT3. The apparent values of K m and V max for the transport by hOAT1 were 4.83 M and 26.0 pmol/ oocyte/h respectively. In rOAT3, the respective values were 6.87 M and 21.7 pmol/oocyte/h. This is the first report on xanthurenic acid transport by OAT1 and OAT3.

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Identification of xanthurenic acid 8- O -β- d -glucoside and xanthurenic acid 8- O -sulfate as human natriuretic hormones

Cited by 23 publications

References 25 publications

Diuresis by intravenous administration of xanthurenic acid in rats, and inhibition by probenecid

Diuresis by intravenous administration of xanthurenic acid in rats, and inhibition by probenecid

Involvement of ST1B Subfamily of Cytosolic Sulfotransferase in Kynurenine Metabolism to Form Natriuretic Xanthurenic Acid Sulfate

Transport of Xanthurenic Acid by Rat/Human Organic Anion Transporters OAT1 and OAT3

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