Differential regulation of canalicular multispecific organic anion transporter (cMOAT) expression by the chemopreventive agent oltipraz in primary rat hepatocytes and in rat liver.
Expression of the canalicular multispecific organic anion transporter (cMOAT), an efflux pump involved in biliary secretion of xenobiotics, was investigated in rat hepatocytes exposed to the chemopreventive agent oltipraz. Northern blotting indicated that this compound increased cMOAT mRNA levels in primary cultured hepatocytes. Such an induction of cMOAT transcripts was demonstrated to be dose-dependent and started as early as 4 h treatment; in addition, western blotting showed increased levels of 190 kDa cMOAT in oltipraz-treated primary rat hepatocytes when compared with their untreated counterparts. In contrast, administration of oltipraz to rats failed to enhance hepatic cMOAT mRNA and protein amounts whereas it was found to induce liver expression of glutathione S-transferase P1, a well-known oltipraz-regulated drug metabolizing enzyme. These data therefore suggest that cMOAT up-regulation occurring in rat hepatocytes in response to oltipraz may be restricted to in vitro situations and is therefore unlikely to be directly involved in the in vivo chemopreventive properties of oltipraz.
Courtois
A
A
INSERM U456 'D¿etoxication et R¿eparation Tissulaire', Facult¿e de Pharmacie, 2 avenue du Pr L. Bernard, 35043 Rennes Cedex, France.
Payen
L
L
Vernhet
L
L
Morel
F
F
Guillouzo
A
A
Fardel
O
O
D000818:Animals; D027321:Anion Transport Proteins; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D002352:Carrier Proteins / Q000235:genetics*; D002478:Cells, Cultured; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D011719:Pyrazines / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013871:Thiones; D013876:Thiophenes; D015854:Up-Regulation
D027321:Anion Transport Proteins; D016588:Anticarcinogenic Agents; D002352:Carrier Proteins; D011719:Pyrazines; D012333:RNA, Messenger; D013871:Thiones; D013876:Thiophenes; C026209:oltipraz