Hydrogen sulfide as an endogenous modulator of biliary bicarbonate excretion in the rat liver

Kimihito Fujii, Tadayuki Sakuragawa, Misato Kashiba, Yasoo Sugiura, Mieko Kondo, Kayo Maruyama, Nobuhito Goda, Yuji Nimura, Makoto Suematsu

研究成果: Article査読

21 被引用数 (Scopus)

抄録

Cystathionine γ-lyase (CSE) is an enzyme catalyzing cystathionine and cysteine to yield cysteine and hydrogen sulfide (H2S), respectively. This study aimed to examine if H2S generated from the enzyme could serve as an endogenous regulator of hepatobiliary function. Gas Chromatographic analyses indicated that, among rat organs herein examined, liver constituted one of the greatest components of H2S generation in the body, at 100 μmol/g of tissue, comparable to that in kidney and 1.5-fold greater than that in brain, where roles of the gas in the regulation of neurotransmission were reported previously. At least half of the gas amount in the liver appeared to be derived from CSE, because blockade of the enzyme by propargylglycine suppressed it by 50%. Immunohistochemistry revealed that CSE occurs not only in hepatocytes, but also in bile duct. In livers in vivo, as well as in those perfused ex vivo, treatment with the CSE inhibitor induced choleresis by stimulating the basal excretion of bicarbonate in bile samples. Transportal supplementation of NaHS at 30 μmol/L, but not that of N-acetylcysteine as a cysteine donor, abolished these changes elicited by the CSE inhibitor in the perfused liver. The changes elicited by the CSE blockade did not coincide with alterations in hepatic vascular resistance, showing little involvement of vasodilatory effects of the gas in these events, if any. These results first provided evidence that H2S generated through CSE modulates biliary bicarbonate excretion and is thus a determinant of bile salt-independent bile formation in the rat liver.

本文言語English
ページ(範囲)788-794
ページ数7
ジャーナルAntioxidants and Redox Signaling
7
5-6
DOI
出版ステータスPublished - 2005 5

ASJC Scopus subject areas

  • 生化学
  • 生理学
  • 分子生物学
  • 臨床生化学
  • 細胞生物学

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