<b>Molecular mechanism of urate-lowering effects of anserine nitrate</b>

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Author(s)

    • Otsuka Yusuke
    • Department of Pharmacology, Chiba University Graduate School of Medicine, Chiba, Japan.|Department of Nephrology, Graduate of Medicine, Nippon Medical School Hospital, Tokyo, Japan.|Department of Pharmacology and Toxicology, Dokkyo Medical University School of Medicine, Tochigi, Japan.
    • Ohno Yuta
    • Department of Pharmacology, Chiba University Graduate School of Medicine, Chiba, Japan.|Department of Pharmacology and Toxicology, Dokkyo Medical University School of Medicine, Tochigi, Japan.|Department of Pharmacy Gifu University, Hospital, Gifu, Japan.
    • Morita Asuka
    • Department of Pharmacology and Toxicology, Dokkyo Medical University School of Medicine, Tochigi, Japan.
    • Otani Naoyuki
    • Department of Pharmacology and Toxicology, Dokkyo Medical University School of Medicine, Tochigi, Japan.
    • Jutabha Promsuk
    • Department of Pharmacology and Toxicology, Dokkyo Medical University School of Medicine, Tochigi, Japan.
    • Ouchi Motoshi
    • Department of Pharmacology and Toxicology, Dokkyo Medical University School of Medicine, Tochigi, Japan.
    • Tsuruoka Shuichi
    • Department of Nephrology, Graduate of Medicine, Nippon Medical School Hospital, Tokyo, Japan.
    • Anzai Naohiko
    • Department of Pharmacology, Chiba University Graduate School of Medicine, Chiba, Japan.|Department of Pharmacology and Toxicology, Dokkyo Medical University School of Medicine, Tochigi, Japan.

Abstract

<p>Recently, anserine (beta-alanyl-3-methyl-L histidine), one of the dipeptides, was reported to lower the serum uric acid level in humans. This level in humans is regulated by the balance between urinary excretion mediated by renal tubular transporters in the kidney and enzymatic production mainly in the liver xanthine oxidase (XO). The mechanism of anserine lowering the serum uric acid level is still unknown, so we investigated it by examining whether anserine inhibits urate excretion or production. To analyze the uricosuric action, we performed a [<sup>14</sup>C]urate uptake experiment in human embryonic kidney cells stably expressing human urate transporter 1 (HEK293- URAT1) or mock (HEK293-mock) cells with 10 mM of the following substrates: beta-alanine, 1-methylL-histidine, 3-methyl-L-histidine, carnosine (betaalanyl-L-histidine), and anserine nitrate. Because only anserine nitrate was commercially available and there was a report that sodium nitrate injected intracellularly increased urate uptake mediated by URAT1, we also examined the effect of sodium nitrate on urate uptake via URAT1. Next, we carried out a XO activity assay to analyze the inhibitory effect on urate production with 10 mM of substrates, as previously mentioned. In the uptake experiment, anserine nitrate and sodium nitrate markedly inhibited urate uptake mediated by URAT1. 3-Methyl-L-histidine and carnosine showed weak inhibitory effects. Beta-alanine and 1-methylL-histidine did not show inhibitory effects. In the XO activity assay, anserine nitrate markedly inhibited XO activity and its IC50 was 6.45 ± 1.57 mM. 3-MethylL-histidine and carnosine showed weak inhibitory effects. Beta-alanine, 1-methyl-L-histidine, and sodium nitrate did not show inhibitory effects. Although the effect of anserine nitrate on URAT1 was unsettled, it showed a marked inhibitory effect on XO activity. This suggests that the effect of anserine to lower the serum urate level in humans is partly due to the inhibition of urate production by XO activity.</p>

Journal

  • GOUT AND NUCLEIC ACID METABOLISM

    GOUT AND NUCLEIC ACID METABOLISM 40(2), 137-143, 2016

    Japanese Society of Gout and Nucleic Acid Metabolism

Codes

  • NII Article ID (NAID)
    130005251395
  • Text Lang
    ENG
  • ISSN
    1344-9796
  • Data Source
    J-STAGE 
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