Membrane P-glycoprotein

Juranka, P. F., Za.stawny, R. L., and Ling, V., 1989. P-Glycoprotein Multidrug-resistance and a superfamily of membrane-a.s.sociated tran.sport protein.s. The FASEByowrna/3 2583-2592. 

P-glycoprotein, a plasma membrane transport protein, is present in the gut, brain, liver, and kidneys 42 This protein provides a biologic barrier by eliminating toxic substances and xenobiotics that may accumulate in these organs. P-glycoprotein plays an important role in the absorption and distribution of many medications. Medications that are CYP3A4 substrates, inhibitors, or inducers are also often affected by P-glycoprotein therefore, the potential for even more DDIs exists in transplant recipients.42... 

Tumor cells may become resistant when genetic changes occur during cell proliferation. Resistant cancer cells with the mdr-1 gene may possess a membrane-associated protein, p-glycoprotein, that facilitates efflux of chemotherapy agents out of the cells. Numerous attempts at blocking this efflux pump have been unsuccessful. 

Chen, Y. Pant, A. C. Simon, S. M., P-glycoprotein does not reduce substrate concentration from the extracellular leaflet of the plasma membrane in living cells, Cancer Res. 61, 7763-7768 (2001). 

J Riordan, V Ling. (1979). Purification of P-glycoprotein from plasma membrane vesicles of Chinese hamster ovary cell mutants with reduced colchicine permeability. J Biol Chem 254 12701-12705. 

N. L. Simmons, and B. H. Hirst. Functional expression of P-glycoprotein in apical membranes of human intestinal Caco-2 cells. Kinetics of vinblastine secretion and interaction with modulators, J. Biol. Chem. 1993, 268, 14991-14997... 

Li, L. Y., Amidon, G. L., Kim, J. S., Heimbach, T.j Kesisoglou, F. et al., Intestinal metabolism promotes regional differences in apical uptake of indinavir coupled effect of P-glycoprotein and cytochrome P450 3A on indinavir membrane permeability in rat, /. Pharmacol. Exp. Ther. 2002, 301, 586-593. 

P-glycoprotein (P-gp) extrudes a wide variety of chemically unrelated endogenous and exogenous compounds out of cell membranes (for a review, see Refs. [1-4]). 

Ferte, J., Analysis of the tangled relationships between P-glycoprotein-mediated multidrug resistance and the lipid phase of the cell membrane, Eur. J. Biochem. 2000, 267, 277-294. 

Shapiro, A. B., Ling, V., Extraction of Hoechst 33342 from the cytoplasmic leaflet of the plasma membrane by P-glycoprotein, Eur. J. Biochem. 1997, 250, 122-129. 

Romsicki, Y., Sharom, F. J., The membrane lipid environment modulates drug interactions with the P-glycoprotein multidrug transporter, Biochemistry 1999, 38, 6887-6896. 

Muller, M., Mayer, R., Hero, U., Keppler, D., ATP-dependent transport of amphiphilic cations across the hepatocyte canalicular membrane mediated by mdrl P-glycoprotein, FEBS Lett. 1994, 343, 168-172. 

P-glycoprotein is not only expressed in tumor cells, but also in cells of several healthy tissues. In liver it was detected in the biliary canalicular surface of hepato-cytes and the apical surface of small biliary ductules. In the small intestine and colon, it is localized in the apical surface of columnar epithelial cells, and in kidneys it is found in the brush border membrane of proximal tubules. Moreover, it is detectable on the apical surface of small ductules in the pancreas and on the surface of cells in the medulla and cortex of adrenals [2]. 

The tissue distribution of P-glycoprotein yields important clues to its function. In most tissues it is localized to the apical (luminal) membrane of polarized epithelial cell layers. This location suggests that P-glycoprotein extrudes its substrates from the epithelial cells into the adjacent lumen. It is anticipated that P-glycopro-tein plays an important role as a protective mechanism against naturally occur-... 

Smith AJ, Timmermans-Hereijgers JL, Roelofsen B, Wirtz KW, van Blitters-wijk WJ, Smit JJ et al. The human MDR3 P-glycoprotein promotes translocation of phosphatidylcholine through the plasma membrane of fibroblasts from transgenic mice. FEBS Lett 1994 354(3) 263—266. 

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