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Effects of Ethanol on L‐Arginine Transport in Rat Ito Cells in Relation to Nitric Oxide Production
Author(s) -
Saibara Toshiji,
Ono Masafumi,
Iwasaki Shinji,
Maeda Takashi,
Onishi Saburo,
Hayashi Yoshihiro,
Enzan Hideaki
Publication year - 2001
Publication title -
alcoholism: clinical and experimental research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 153
eISSN - 1530-0277
pISSN - 0145-6008
DOI - 10.1111/j.1530-0277.2001.tb02416.x
Subject(s) - hepatic stellate cell , nitric oxide , arginine , nitric oxide synthase , extracellular , tumor necrosis factor alpha , chemistry , medicine , biochemistry , endocrinology , microbiology and biotechnology , biology , amino acid
Background: Nitric oxide (NO) is a potent mediator of hepatic sinusoidal hemodynamics that is synthesized in the hepatic stellate cells (Ito cells, fat‐storing cells) and affects these cells. NO production may depend on the induction of inducible nitric oxide synthase and on transport of extracellular L‐arginine. The precise mechanism that controls NO production in stellate cells was characterized recently. Methods: Kinetic analysis of L‐arginine transport and reverse transcription‐polymerase chain reaction for cationic amino acid transporter (CAT) were carried out by using stellate cells prepared from the male Wistar rat. The effect of ethanol on L‐arginine transport and NO production of stellate cells was assessed in the presence of tumor necrosis factor (TNF)‐α and interferon (IFN)‐γ. Results: The L‐arginine transport system functioning in the hepatic stellate cells was system y+, possibly mediated by CAT‐1 and CAT‐2B ( K m ∼50 μM). IFN‐γ in combination with TNF‐α induced NO production with an enhancement in CAT‐2B mRNA expression and L‐arginine transport, whereas L‐arginine transport and NO production were suppressed by coincubated ethanol. Conclusions: In hepatic stellate cells, ethanol has suppressive effects on NO production and extracellular L‐arginine transport in the presence of TNF‐α and IFN‐γ. The estimated K m of L‐arginine transporter in hepatic stellate cells is very similar to the physiological L‐arginine concentration in portal vein. Our findings may support the merit of further studies on the modulation of NO production via access to portal blood L‐arginine concentration to control disturbed hepatic sinusoidal blood flow in patients with alcoholic liver disease.