1993 Fiscal Year Final Research Report Summary
HEPAIOCYTE MEMBRANE TRANSPORT MECHANISM OF VARIOUS SUBSTANCES
| Project/Area Number |
04454247
|
|---|
| Research Category |
Grant-in-Aid for General Scientific Research (B)
|
| Allocation Type | Single-year Grants |
|---|
| Research Field |
Gastroenterology
|
|---|
| Research Institution | SECOND DEPARTMENT OF INTERNAL MEDICINE.KINKI UNIVERSITY SCHOOL OF MEDICINE. |
|---|
Principal Investigator |
YAMAMOTO Toshio KINKI UNIVERSITY SCHOOL OF MEDICINE.SECOND DEPARTMENT OF INTERNAL MEDICINE, PROFESSOR., 医学部, 教授 (50088522)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
ADACHI Yukihiko KINKI UNIVERSITY SCHOOL OF MEDICINE.SECOND DEPARTMENT OF INTERNAL MEDICINE, ASSO, 医学部, 助教授 (50111026)
|
|---|
| Project Period (FY) |
1992 – 1993
|
| Keywords | BILIARY EXCRETION / ATP / ORGANIC ANION / JAUNDICE / HYPERBILIRUBINEMIA / BILE ACIDS / DUBIN-JOHNSON SYNDROME / PRAVASTATIN |
|---|
| Research Abstract |
(1)Canalicular membrane vesicles (CMV) of hepatocytes were prepared in pure form from the livers of normal SD rats and Eisai hyperbilirubinuric rats (HEBR). Mg^<++> -ATPase and alkaline phosphatase activities were highly enriched in the CMV.[ ^3H]Bilirubin diglucuronide (BDG) was purified from the hile of rats injected with [ ^3H]DELTA ALA.
(2)Transport of [ ^3H]BDG and [ ^3H]taurocholate (TC) was observed using CMV from livers of SD rats and EHBR, and any differences of their transport between the 2 rat strains were compared. ATP-dependent [ ^3H]TC transport was present both in SD rat CMV and EHBR CMV.On the other hand, [ ^3H]BDG transport was not ATP-dependent and was increased in the presence of bicarbonate ion. This bicarbonate-dependent [ ^3H]BDG transport was also intact in EHBR CMV.
(3)[^<14>C]Pravastatin (PS), One of model organic anions, is excreted in the bile of SD rats. However, its biliary excretion was found to be extremely delayd in EHBR.[^<14>C]PS transport by SD rat CMV was studied and found to be ATP-dependent. In contrast to the in vivo biliary excretion defect of PS, normal ATP-dependent PS transport was found in EHBR CMV.
(4)From these results. the postulated defect in ATP-dependent organic anion transport in congenitally jaundiced EHBR was not confirmed and the presence of a novel ATP-dependent organic anion transporter was suugested on the canalicular membrane of rat hepatocytes.
|
