Related Experiment Video
Updated: Jul 16, 2026
Models and Methods to Evaluate Transport of Drug Delivery Systems Across Cellular Barriers
Published on: October 17, 2013
Mitoxantrone permeability in MDCKII cells is influenced by active influx transport
Guoyu Pan1, William F Elmquist
1Department of Pharmaceutics, University of Minnesota, 308 Harvard Street SE, Minneapolis, Minnesota 55455, USA.
Abstract:
Mitoxantrone (MXR) is a prototypical substrate for the ABCG2 (bcrp1) efflux transporter and is often used as a positive control in bcrp-mediated transport studies. This study examined processes involved in the cellular accumulation and directional transport of MXR using an in vitro wild-type (WT) and bcrp1-transfected (bcrp1) MDCKII cell model. Compared to 37 degrees C, incubation at 4 degrees C increased MXR accumulation in bcrp1 cells and unexpectedly decreased MXR accumulation in WT MDCKII cells. [3H]-MXR accumulation was concentration dependent in both WT and bcrp1 cells, exhibiting the characteristics of saturable active influx. At tracer concentrations, there was no difference in MXR directional flux between WT and bcrp1 MDCKII cell monolayers, and the A-to-B (apical-to-basolateral) flux was greater than the B-to-A flux in both cell types. However at higher concentration (20 microM), [3H]-MXR directional flux from A to B decreased and B to A increased, revealing the expected efflux process. Therefore, the orientation of the MXR directional flux process is concentration dependent and only at higher concentrations could the difference between WT and bcrp1 MDCKII cells be distinguished. Taken together, these data show that there is a saturable influx transport system on the apical membrane MDCKII cells that is responsible for the active influx of MXR. This is the first report of an active influx transport system for MXR. The expression of the putative MXR influx transporter in selected cell types could lead to misleading results in drug transport assays that screen for bcrp activity. Moreover, the downregulation of the influx transport system could be a heretofore unrecognized mechanism of MXR resistance in tumor cells.
Related Concept Videos
01:06Carrier-Mediated Transport
Active transport involves two types of membrane-spanning transporters: uptake and efflux. Uptake transporters are expressed in the small...
01:24Cellular Membranes and Drug Transport
Phospholipids arrange themselves into a bilayer, with hydrophilic heads oriented outward and hydrophobic tails facing inward.
01:17Pore Transport and Ion-Pair Transport
Pore transport, also known as convective transport, is a process where small molecules like urea, water, and sugars rapidly cross cell membranes as though there were channels or pores in the membrane. Although direct microscopic evidence is limited but the concept of pores or channels is widely accepted based on physiological evidence. Despite the lack of direct microscopic...
01:23Mechanisms of Drug Absorption: Paracellular, Transcellular, and Vesicular Transport
However, most drugs use the transcellular route, traversing directly through the cell membranes via two mechanisms: passive and active transport. Passive...
01:23Drug Absorption Mechanism: Passive Membrane Transport
01:14Active Transport
Primary active transporters, like Na+, K+ and -ATPase, directly utilize ATP to move ions across the membrane. These transporters play significant roles in various physiological processes. For instance, Na+, K+ and -ATPase maintain...