Contribution of radixin to P‐glycoprotein expression and transport activity in mouse small intestine in vivo. Issue 8 (10th June 2013)

• Record Type: Journal Article
• Authors: Yano, Kentaro; Tomono, Takumi; Sakai, Riyo; Kano, Takashi; Morimoto, Kaori; Kato, Yukio; Ogihara, Takuo
• Is Part Of: Journal of pharmaceutical sciences. Volume 102:Issue 8(2013:Aug.)
• Page Start: 2875
• Page End: 2881
• Publication Date: 2013-06-10
• Subjects: ERM proteins -- radixin -- P‐glycoprotein -- Efflux pumps -- Intestinal secretion/transport -- Absorption -- Pharmacokinetics -- in vivo -- knockout mice; Pharmacy -- Periodicals; 615.1
• DOI: 10.1002/jps.23637
• Languages: English
• ISSNs: 0022-3549

Abstract

Abstract: The ERM proteins, ezrin, radixin, and moesin, are membrane‐cytoskeleton cross‐linkers 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