MDR1-MDCK

P-gp substrate 63 substrates and 35 substrates and 94% substrates and Transport MDR1-MDCK High probability to be a [50]... 

Zhang Y, Benet LZ. Characterization of P-glycoprotein mediated transport of K02, a novel vinylsulfone peptidomimetic cysteine protease inhibitor, across MDR1-MDCK and Caco-2 cell monolayers. Pharm Res 1998 15(10) 1520-1524. 

The MDR1-MDCK transport assay was evaluated by Polli et al. (2001). The scientist compared the Pgp transport assay with the calcein-AM and ATPase... 

Tang, F., K. Horie, and R. T. Borchardt. Are MDCK cells transfected with the human MDR1 gene a good model of the human intestinal mucosa , Pharm. Res. 2002, 29, 765-772... 

In the transport assays, the permeability of a compound in both absorption and secretion directions is measured using polarized epithelial cells that constitutively express high levels of P-gp (e.g. Caco-2) or have been transfected with the gene for a specific P-gp (e.g. MDR1-transfected MDCK or LLC-PK1 cells). Since P-gp is expressed on the apical membrane, ratios ofbasolateral-to-apical (B —> A) permeability versus apical-to-basolateral (A —> B) permeability greater than 1 may indicate an active efflux transport process. Bidirectional permeability measurements can also be performed in the presence of a specific P-gp inhibitor. Thus, apical-to-basolateral permeability increases and basolateral-to-apical permeability decreases such that... 

Pastan I, Gottesman MM, Ueda K, et al. A retrovirus carrying an MDR1 cDNA confers multidrug resistance and polarized expression of P-glycoprotein in MDCK cells. Proc Natl Acad Sci U S A 1988 85(12) 4486 I490. 

Soldner A, Benet L, Mutschler E, Christians U (2000) Active transport of the angiotensine II antagonist losartan and its main metabolite EXP 3174 across MDCK-MDR1 and CACO-2 cell monolayers. Br J Pharmacol 129 1235-1243... 

One further point has to be taken into account which is generally valid for cell-based assays the background expression of endogenous canine transporters. In case of MDCK cells especially the efflux transporter MRP2 and Pgp (MDR1) are strongly expressed. Kidney specific organic anion transporters (OATs) will be present as well. 

Figure 7.2 Studies of specific drug transport routes in multifunctional cell models such as Caco-2 cells may be complicated, as there is a lack of specific substrates for many drug transporters. Therefore, specialized cell models that accommodate mainly passive (2/4/A1) or selected active (MDCK-MDR1) transport pathways are preferred in some cases.

The inherent enzymatic activity seems low also in other cell lines used for screening, such as MDCK and LLC-PK1 cells [158], Both MDCK and LLC-PK1 cells have been transfected with CYP3A4 and MDR1 for studying the concert action between dmg metabolism and secretion via efflux transporters [158]. 

MDCK Madin-Darby canine kidney cell line used as absorption model MDR1 Multidrug resistance protein 1 (also designated P-gp and ABCB1)... 

Using putative MDR1 substrates, MDCK cells express substantially higher levels of native efflux transporters than those of LLC-PKi cells. Everything else being equal, the LLC-PKi model is preferred because it forms high-quality monolayers and has low levels of native transporters. 

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