PT  - JOURNAL ARTICLE
AU  - Emilie Jigorel
AU  - Marc Le Vee
AU  - Claire Boursier-Neyret
AU  - Marc Bertrand
AU  - Olivier Fardel
TI  - FUNCTIONAL EXPRESSION OF SINUSOIDAL DRUG TRANSPORTERS IN PRIMARY HUMAN AND RAT HEPATOCYTES
AID  - 10.1124/dmd.105.004762
DP  - 2005 Oct 01
TA  - Drug Metabolism and Disposition
PG  - 1418--1422
VI  - 33
IP  - 10
4099  - http://dmd.aspetjournals.org/content/33/10/1418.short
4100  - http://dmd.aspetjournals.org/content/33/10/1418.full
SO  - Drug Metab Dispos2005 Oct 01; 33
AB  - Primary hepatocyte cultures are considered as a useful in vitro system for pharmacological/toxicological studies. Although expression of drug-metabolizing enzymes and canalicular drug transporters has been well documented in this cellular model, less information is available about sinusoidal drug transporter activities. This has led us to investigate functional expression of the major sinusoidal transporters in primary human and rat hepatocytes. Using radiolabeled substrates and chemical transporter inhibitors, activities of organic cation transporter 1, organic anion-transporting polypeptides, organic anion transporter 2, and Na+-taurocholate cotransporter were detected in cultured human and rat hepatocytes. In parallel, mRNA expression of these transporters was demonstrated using reverse transcriptase-quantitative polymerase chain reaction assays. Functional expression of sinusoidal transport proteins markedly decreased with time in primary rat hepatocyte cultures; by contrast, it remained relatively constant in primary human hepatocytes all along the culture, illustrating the fact that liver-specific functions, including drug-detoxifying pathways, are usually better preserved in cultured human hepatocytes than in their rodent counterparts. Primary hepatocytes, especially human hepatocytes, thus exhibit a pattern of sinusoidal transporter expression close to that found in vivo, highlighting the interest of hepatocyte cultures for drug detoxification studies. The American Society for Pharmacology and Experimental Therapeutics