DMD Highlight: Microvilli Morphology Can Affect Efflux Active P-Glycoprotein in Confluent MDCKII -hMDR1-NKI and Caco-2 Cell Monolayers
P-glycoprotein (P-gp) is expressed in both confluent MDCKII-hMDR1-NKI and Caco-2 cell monolayers. In Caco-2 cells, total P-gp was about 10-fold greater than efflux active P-gp, compared to only a two-fold difference in MDCKII-hMDR1-NKI cells. 3D structured illumination super-resolution microscopy showed that the microvilli in Caco-2 cells are taller and more densely packed than those in MDCK-hMDR1-NKI cells. Thus a substantial fraction of P-gp cannot contribute to final release of drug into the apical chamber. These results suggest that the effect of microvilli morphology differences between in vitro and in vivo systems must be considered when scaling transporter activity for efflux transporters of amphipathic compounds, for example, P-gp.
See the article by Meng et al. at Drug Metabolism and Disposition February 2017, 45 (2) 145-151; DOI: https://doi.org/10.1124/dmd.116.072157