Related Experiment Video
Updated: Jan 10, 2026

An Intestine/Liver Microphysiological System for Drug Pharmacokinetic and Toxicological Assessment
Published on: December 3, 2020
Expression of Selected Pharmacologically Relevant Transporters in Murine Non-Parenchymal Liver Cells Compared to
Vincent Rönnpagel1, Anett Ullrich2, Christy Joseph1
1Institute for Pharmacology, Center of Drug Absorption and Transport (C_DAT), University Medicine Greifswald, Felix-Hausdorff-Str. 3, 17487 Greifswald, Germany.
Abstract:
Primary hepatocytes are widely used in preclinical drug development, with their transporter expression being well-characterized. However, less is known about non-parenchymal liver cells (NPCs), which constitute 40% of the liver's cell population and include sinusoidal endothelial cells and Kupffer cells. This study aimed to characterize transporter expression in murine NPCs compared to hepatocytes. Cell fractions were isolated using collagenase perfusion, density gradient centrifugation, and magnetic-activated cell sorting (MACS) with F4/80 and CD146 antibodies. Transporter expression and separation quality were analyzed via RT-qPCR. Results showed NPC-specific genes were significantly lower in hepatocytes and vice versa. Importantly, NPCs exhibited higher expression of several transporters: Abcc1/Mrp1 (87-fold), Abcc4/Mrp4 (4-fold), Abcc5/Mrp5 (40-fold), as well as Slc15a2/PepT2 (16-fold), Slc28a2/Cnt2 (20-fold), Slco3a1/Oatp3a1 (15-fold), and Slco4a1/Oatp4a1 (13-fold), compared to hepatocytes. Hepatocytes showed dominant expression of Abcc2/Mrp2, Abcg2/Bcrp, Slc22a1/Oct1, and others. Minimal differences in transporter expression were found between Kupffer and endothelial cells. In conclusion, the efflux transporters Abcc1/Mrp1 and Abcc5/Mrp5 are predominantly expressed in NPCs. This suggests that NPCs are potentially relevant for the transport of certain drugs and should be included in in vitro preclinical testing.
Related Concept Videos
Hepatic Drug Clearance: Role of Transporters
Physiological Pharmacokinetic Models: Incorporating Hepatic Transporter-Mediated Clearance
A recent model describes pravastatin's hepatobiliary excretion,...
Carrier-Mediated Transport
Active transport involves two types of membrane-spanning transporters: uptake and efflux. Uptake transporters are expressed in the small...
Nonlinear Pharmacokinetics: Role of Transporters
Polymorphisms occurring in drug transporters can alter...
Cell Specific Gene Expression
Effect of Hepatic Disease on Pharmacokinetics: Pathophysiologic Assessment and Liver Function Test

