1995 Fiscal Year Final Research Report Summary
Roles of low molecular ononoxides in regulation of hepatobiliary function
| Project/Area Number |
06454264
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Gastroenterology
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| Research Institution | Keio University School of Medicine |
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Principal Investigator |
SUEMATSU Makoto Dept Biochem.Keio Univ.Ass Professor., 医学部, 専任講師 (00206385)
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| Co-Investigator(Kenkyū-buntansha) |
WATANABE Norihito Dept.Med.Tokai Univ.Ass Professor., 医学部, 助教授 (90167156)
ISHIMURA Yuzuru Dept Biochem.Keio Univ.Professor., 医学部, 教授 (40025599)
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| Project Period (FY) |
1994 – 1995
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| Keywords | carbon monoxide / nitric oxide / heme oxygenase / microcirculation / Ito cell / liver / cholestasis / bilirubin |
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| Research Abstract |
Heme oxygenase is a heme-oxidizing enzyme which generates biliverdin and carbon monoxide (CO). The present study was designed to elucidate whether CO endogenously produced by this enzyme serves as an active vasorelaxant in the hepatic microcirculation. Microvasculature of the isolated perfused rat liver was visualized by dual-color digital microfluorography to monitor sinusoidal lining and fat-storing Ito cells, alternately. In the control liver, the CO flux in the venous effluent ranged at 0.7 nmol/min /g liver. Administration of a heme oxygenase inhibitor zinc protoporphyrin IX (1 muM) eliminated the baseline CO generation, and the vascular resistance exhibited a 30% elevation concurrent with discrete patterns of constriction in sinusoids and reduction of the sinusoidal perfusion velocity. The major sites of the constriction corresponded to local sinusoidal segments colocalized with Ito cells which were identified by imaging their vitamin A autofluorescence. The increase in the vascular resistance and sinusoidal constriction were attenuated significantly by adding CO (1 muM) or a cGMP analogue 8-bromo-cGMP (1 muM) in the perfusate. From these findings, we propose that CO can function as an endogenous modulator of hepatic sinusoidal perfusion through a relaxing mechanism involving Ito cells.
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[Publications] Suematsu, M., Kashiwagi, S., Sano, T., Goda, N., Shinoda, Y., Ishimura, Y.: "Carbon monoxide as an endogenous modulator of hepatic vascular perfusion" Biochem.Biophys.Res.Commun. 205. 1333-1337 (1994)
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「研究成果報告書概要(欧文)」より
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[Publications] Suematsu, M., Goda, N., Sano, T., kashiwagi, S., Egawa, T., Shinoda, Y., Ishimura, Y.: "Carbon monoxide : An endogenous modulator of sinusoidal tone in the perfused rat liver." J.Clin.Invest.96. 2431-2437 (1995)
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「研究成果報告書概要(欧文)」より
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[Publications] Yamaguchi, T., Wakabayashi, Y., Tanaka, M., Sano, T., Ishikawa, H., Nakajima, H., Suematsu, M., Ishimura, Y.: "Taurocholate is necessary for directional excretion bilirubin into bile in the perfused rat liver." Am.J.Physiol. (Gastrointest.& Liver Physiol.). (in press). (1996)
Description
「研究成果報告書概要(欧文)」より
