REGULATION OF ORGANIC ANION TRANSPORT IN THE LIVER

Citation
H. Roelofsen et al., REGULATION OF ORGANIC ANION TRANSPORT IN THE LIVER, The Yale journal of biology & medicine, 70(4), 1998, pp. 435-445
Citations number
69
Categorie Soggetti
Medicine, Research & Experimental
ISSN journal
00440086
Volume
70
Issue
4
Year of publication
1998
Pages
435 - 445
Database
ISI
SICI code
0044-0086(1998)70:4<435:ROOATI>2.0.ZU;2-C
Abstract
In several liver diseases the biliary transport is disturbed, resultin g in, for example, jaundice and cholestasis. Many of these symptoms ca n be attributed to altered regulation of hepatic transporters. Organic anion transport, mediated by the canalicular multispecific organic an ion transporter (cmoat), has been extensively studied. The regulation of intracellular vesicular sorting of cmoat by protein kinase C and pr otein kinase A, and the regulation of cmoat-mediated transport in endo toxemic liver disease, have been examined. The discovery that the mult idrug resistance protein (MRP), responsible for multidrug resistance i n cancers, transports similar substrates as cmoat led to the cloning o f a MRP homologue from rat liver, named mrp2. Mrp2 turned out to be id entical to cmoat. At present there is evidence that at least two mrp's are present in hepatocytes, the original mrp (mrp1) on the lateral me mbrane, and mrp2 (cmoat) on the canalicular membrane. The expression o f mrp1 and mrp2 in hepatocytes appears to be cell-cycle-dependent and regulated in a reciprocal fashion. These findings show that biliary tr ansport of organic anions and possibly other canalicular transport is influenced by the entry of hepatocytes into the cell cycle. The clonin g of the gene for cmoat opens up new possibilities to study the regula tion of hepatic organic anion transport.