2005 Fiscal Year Final Research Report Summary
A study on the vesicular transport of canalicular transporters
| Project/Area Number |
16590634
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Gastroenterology
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| Research Institution | Teikyo University |
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Principal Investigator |
TAKIKAWA Hajime Teikyo Univ., Dept.of Medicine, Professor, 医学部, 教授 (70197226)
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| Project Period (FY) |
2004 – 2005
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| Keywords | bile acid / organic anion / organic cation / transporter / vesicular transport / biliary excretion / colchicine / Bsep |
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| Research Abstract |
Colchicine, an inhibitor of the intracellular vesicular transport, has been reported to inhibit the biliary excretion of bile acids and organic anions, but the previous findings are controversial.
In order to systematically evaluate the effect of colchicine on the biliary excretion of cholephilic compounds, we studied the effect of colchicines on the biliary excretion of substrates of various canalicular transporters. Substrates of various canalicular transporters were infused at the rate of or above their excretory maximum into rats, and the effect of colchicine on their biliary excretion was studied. The biliary excretion of taurocholate was markedly inhibited by colchicine, whereas that of tauroursodeoxycholate was not inhibited.
The biliary excretory maximum of taurolithocholate-sulfate and sulfobromophthalein, substrates of mrp2, that of erythromycin, a substrate of P-gp were not affected by colchicine.
The different excretory maximum of taurocholate and tauroursodeoxycholate and the different effect of colchicine on the excretion of these bile acids are considered to be different regulatory mechanisms of vesicular targeting of the Bsep to the canalicular membrane by these bile acid conjugates. The vesicular targeting of Mrp2 and the P-gp to the canalicular membrane is considered to be colchicine insensitive in the absence of bile acid coadministration.
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