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.