| Project/Area Number |
60570322
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Gastroenterology
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| Research Institution | Tottori University |
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Principal Investigator |
IKAWA Shiro Division of Chemiatry, Institute of Steroid Research Tottori University School of Medicine, Professor, 医学部, 教授 (70032183)
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| Co-Investigator(Kenkyū-buntansha) |
MIYAKE Mariko Division of Chemistry, Institute of Steroid Research Tottori University School o, 医学部附属ステロイド医学研究施設・化学部門, 助手 (20135883)
MURA Tetuo Division of Chemistry, Institute of Steroid Research Tottori University School o, 医学部附属ステロイド医学研究施設・化学部門, 講師 (80093631)
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| Project Period (FY) |
1985 – 1986
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| Project Status |
Completed (Fiscal Year 1986)
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| Budget Amount *help |
¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 1986: ¥300,000 (Direct Cost: ¥300,000)
Fiscal Year 1985: ¥1,100,000 (Direct Cost: ¥1,100,000)
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| Keywords | Bile acid uptake / Primary culture / Rat hepatocyte / Estradiol-glucuronide / Bile acid metabolism / <Na^+> , <K^+> -ATPase / 【Na^+】,【K^±】ATPase |
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| Research Abstract |
Bile acid uptake mechanism of the hepatocytye membrane was studied using primary cultured rat hepatocytes. Bile acid profiles of intra or extrahepatocyte, namely the hepatocyte or the culture medium were used as the indicator showing the biochemical functions of the hepatocyte.
Bile acid profiles of primary cultured rat hepatocytes were kept qualitatively and quantitatively nearly constant during 19-hr to 72-hr incubation. At these incubation periods, bile acid profiles of the incubation medium were most similar to those of the hepatic bile acids of the hepatic bile obtained about 11 hrs after bile duct canulation, regarded as the wash-out point at which point, the bile contains only primary bile acids. The present studies were carried out using the primary cultured rat hepatocytes obtained after 24-hr incubation.
The hepatocytes pretreated with lidocaine hydrochloride of rifamycin reduced bile acid uptake by about 30 to 50 % as compared with the control. On the other hand, the simultane
… More
ous addition albumin with the abovementioned drugs increased bile acid uptake dose-dependently. These facts suggest strongly that the hepatocyte membrane has a bile acid receptor sharing with albumin or these drugs. In the hepatocytes cultured with insulin alone or both dexamethasone and insulin the latter produced and extreted much more taurine-conjugated bile acids. Estradiol-17 <beta> -glucuronide ( <E_2> -17G ) induced the cholestasis-like state: The decrease of intracellular cAMP, 5'-Nase activity and taurine-conjugated bile acids and the marked increase of sulfated bile acids, especially lithocholic and chenodeoxycholic acids were observed, while dexamethasone improved these changes to the normal levels. It seems likely that <E_2> -17G affects endoplasmic reticulumn and peroxisomes in the hepatocyte and causes an alternative pathway of bile acid biosynthesis influencing cholic acid: CoA ligase and 12 <alpha> -hydroxylase and these changes resuly in inhibition of <Na^+> -dependent bile acid reflux followed by the decrease of cAMP-dependent <Na^+> , <K^+> -ATPase, finally induce intrahepatic cholestasis.
Further studies on purification and kinetics of a bile acid receptor on the hepatocyte membrane are required and some are under progress. Less
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