P-glycoprotein pump

Michelson S, Slate D. A mathematical model of the P-glycoprotein pump as a mediator of multidmg resistance. Bull Math Biol 1992 54(6) 1023-1038. 

What is the P-glycoprotein pump and how would it affect oral drag absorption ... 

Hegewisch-Becker, S., Faltz, C., and Hossfeld, D. K. (1996) Prolongation of medium exchange is associated with a decrease in function but not expression of the P-glycoprotein pump in leukaemic cells. Eur. J. Haematol. 56,12-22. 

Figure 5.22 Structure of the P-glycoprotein pump, which confers multidrug resistance to tumor cells, (a) Schematic structure of the P-glycoprotein pump.

Antimalarial blood schizonticide used for treatment and as a chemosuppres-sant where P falciparum is susceptible. Binds to hemin, causing dysfunctional cell membranes resistance due to efflux via P-glycoprotein pump. Tox ... 

Bunting KD, Zhou S, Lu T, Brian P. Enforced P-glycoprotein pump function in murine bone marrow cells results in expansion of side population stem cells in vitro and repopulating cells in vivo. Blood 2000 96 902-909. 

Hendrikse NH, Schinkel AH, de Vries EG, Fluks E, van der Graaf WT, Willemsen AT et al. Complete in vivo reversal of P-glycoprotein pump function in the blood-brain barrier visualized with positron emission tomography. Br J Pharmacol 1998 124 1413-1418. 

P-glycoprotein (P-gp) works as a transporter at the intestinal mucosa pumping drugs out into the lumen. Absorption of P-gp substrates, such as digoxin, cyclosporine, etc., can be increased by inhibitors of P-gp and reduced by inducers. 

Both influx and efflux transporters are located in intestinal epithelial cells and can either increase or decrease oral absorption. Influx transporters such as human peptide transporter 1 (hPEPTl), apical sodium bile acid transporter (ASBT), and nucleoside transporters actively transport drugs that mimic their native substrates across the epithelial cell, whereas efflux transporters such as P-glycoprotein (P-gp), multidrug resistance-associated protein (MRP), and breast cancer resistance protein (BCRP) actively pump absorbed drugs back into the intestinal lumen. 

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. 

P Saha, J Yang, VHL Lee. (1998). Existence of a p-glycoprotein drug efflux pump in cultured rabbit conjunctival epithelial cells. Invest Opthalmol Vis Sci 39 1221-1226. 

Wang Y, Hao D, Stein WD, Yang L (2006) A kinetic study of Rhodamine 123 pumping by P-glycoprotein. Biochim Biophys Acta 1758 1671-1676... 

The use of Caco-2 cell monolayers has gained in popularity as an in vivo human absorption surrogate moreover, the monolayers are generally accepted as a primary absorption screening tool by several pharmaceutical companies [10]. However, Caco-2 cell permeability measurements exhibit certain limitations due to the mechanisms involved. Both passive and active pathways exist active transport tends to increase the absorption across the cells and, since Caco-2 cells overexpress the P-glycoprotein (P-gp) efflux pump, the absorption of some compounds across these cells may be underestimated. 

The sister of P-glycoprotein represents the canalicular bile salt export pump of mammalian liver. J Biol Chem 1998 ... 

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