Contribution of Radixin to P-Glycoprotein Expression and Transport Activity in Mouse Small Intestine In Vivo

The ERM proteins, ezrin, radixin, and moesin, are membrane-cytoskeleton crosslinkers with multiple physiological functions. We previously showed that radixin is involved in posttranslational regulation of P-glycoprotein (P-gp) in human hepatoblastoma HepG2 cells. Here, we investigated the physiological role of radixin in regulating P-gp expression and activity in the small intestine by comparing wild-type- and radixin knockout (Rdx) mice. In intestinal tissue homogenates, P-gp protein levels increased markedly from the upper part to the lower part of the small intestine in both wild-type- and Rdx−/− mice. In the membrane fractions, a similar pattern was seen in wild-type mice. However, the membrane expression of P-gp protein remained at the same level from the upper to the lower part of the small intestine in Rdx−/− mice. When rhodamine123 (Rho123), a substrate of P-gp, was orally administered to Rdx−/− and wild-type mice, the absorption phase of Rho123 was greater in Rdx−/− than in wild-type mice, whereas the elimination phase in Rdx−/− mice was not different from that of wild-type mice. Our results indicate that radixin plays an important role in regulating P-gp localization and P-gp functional activity at the intestinal membrane. © 2013 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 102:2875-2881, 2013