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Expression of basolateral and canalicular transporters in rat liver and cultures of primary hepatocytes

 
: Borlak, J.; Klutcka, T.

:

Xenobiotica 34 (2004), Nr.11/12, S.935-947
ISSN: 0049-8254
Englisch
Zeitschriftenaufsatz
Fraunhofer ITEM ()
Liver; Liver cells; Transportation

Abstract
1. Basolateral and canalicular proteins are expressed in the liver and besides their role in the transport of bilirubin, glutathione, hormones and various glucuronides, they also function as transporters of a wide range of drugs.
2. Despite their frequent use in drug research, little is known about the expression of genes coding for transporters in cultures of primary sandwiched hepatocytes.
3. The kinetics of gene expression of canalicular and basolateral membrane transporters in cultures of primary rat sandwiched hepatocytes were investigated, and the expression of cMOAT, spgp, mdr1a and mdr2 were shown to be comparable with transcript levels observed in vivo.
4. Strikingly, expression of the basolateral membrane transporter ntcp and oatp1 and 2 were dramatically reduced, the level being <10 and <5%, respectively, of those found in vivo in rat liver tissue.
5. Notably, mRNA expression of the canalicular membrane transporter mdr1b was increased up to 13-fold.
6. The findings point to a dramatic change in the expression of basolateral and canalicular transporters in cultured hepatocytes, and this should be considered when hepatocytes are used for drug profiling studies.

: http://publica.fraunhofer.de/dokumente/N-27419.html