Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.6.3.44 (P-glycoprotein)
 13,344 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The relationship between mammalian facilitative glucose transport proteins (GLUT) and multidrug resistance was examined in two vincristine (VCR)-selected murine erythroleukaemia (MEL) PC4 cell lines. GLUT proteins, GLUT1 and GLUT3, were constitutively coexpressed in the parental cell line and also in the VCR-selected cell lines. Increased expression of the GLUT1 isoform was noted both in the PC-V40 (a non-P-glycoprotein, mrp-overexpressing subline) and in the more resistant PC-V160 (overexpressing mrp and mdr3) cell lines. Overexpression of GLUT3 was detected only in the PC-V160 subline. An increased rate of facilitative glucose transport (Vmax) and level of plasma membrane GLUT protein expression paralleled increased VCR resistance, active VCR efflux and decreased VCR steady-state accumulation in these cell lines. Glucose transport inhibitors (GTIs), cytochalasin B (CB) and phloretin blocked the active efflux and decreased steady-state accumulation of VCR in the PC-V40 subline. GTIs did not significantly affect VCR accumulation in the parental or PC-V160 cells. A comparison of protein sequences among GLUT1, GLUT3 and MRP revealed a putative cytochalasin B binding site in MRP, which displayed 44% sequence similarity/12% identity with that previously identified in GLUT1 and GLUT3; these regions also exhibited a similar hydropathy plot pattern. The findings suggested that CB bound to MRP and directly or indirectly lowered VCR efflux and/or CB bound to one or both GLUT proteins, which acted to lower the VCR efflux mediated by MRP. This is the first report of a non-neuronal murine cell line that expressed GLUT3.
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PMID:Effect of glucose transport inhibitors on vincristine efflux in multidrug-resistant murine erythroleukaemia cells overexpressing the multidrug resistance-associated protein (MRP) and two glucose transport proteins, GLUT1 and GLUT3. 901 20

Syncytiotrophoblasts play an essential role in restriction of drug delivery through the blood-placenta barrier (BPB). Conditionally immortalized syncytiotrophoblast cell lines, TR-TBTs, were established at gestational day 18 from pregnant transgenic rats (Tg-rats) harboring the temperature-sensitive SV 40 (ts SV40) large T-antigen. TR-TBTs exhibit temperature-sensitive cell growth due to the expression of SV 40 large T-antigen, and thus the cell growth can be regulated by changing the culture temperature. TR-TBTs exhibit typical properties of syncytiotrophoblast cells, such as syncytium-like morphology, the expression of cytokeratins and hormones, and polarized expression of glucose transporter 1 (GLUT1) and GLUT3. TR-TBTs express in vivo influx and efflux transporters, such as taurine transporter (TauT), betaine/GABA transporter (BGT-1), amino acid transporter 2 (ATA2), organic anion transporting polypeptide 2 (oatp2), organic cation/carnitine transporter (OCTN2), P-glycoprotein (P-gp), and breast cancer resistance protein (BCRP/ABCG2). Moreover, TR-TBTs exhibit taurine, GABA, and DHEA-S uptake activity via TauT, BGT-1, and oatp2, respectively. Therefore, TR-TBTs can be used for the analysis of these functions and would be a good in vitro models for investigating carrier-mediated transport functions at the BPB.
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PMID:Conditionally immortalized syncytiotrophoblast cell lines as new tools for study of the blood-placenta barrier. 1518 10

Cynomolgus monkey has been used as a model for the prediction of drug disposition in human brain. The purpose of this study was to clarify protein expression levels of membrane proteins affecting drug distribution to brain, such as transporters, receptors, and junctional proteins, in cynomolgus monkey brain microvessels by using liquid chromatography tandem mass spectrometry. In adult monkeys, three ATP-binding cassette transporters (multidrug resistance 1 (MDR1), breast cancer resistance protein (BCRP), and multidrug resistance protein 4 (MRP4)), six solute carrier transporters (glucose transporter 1 (GLUT1), GLUT3/14, monocarboxylate transporter 1 (MCT1), MCT8, organic anion transporting polypeptide 1A2, and equilibrative nucleoside transporter 1), two junctional proteins (claudin-5 and vascular endothelial cadherin), and two receptors (insulin receptor and low-density lipoprotein receptor-related protein 1) were detected. Comparison of the expression levels with those in mouse, which we reported previously, revealed a pronounced species difference. BCRP expression in monkey was greater by 3.52-fold than that in mouse, whereas MDR1 and MRP4 expression levels in monkey were lower by 0.304- and 0.180-fold, respectively, than that in mouse. This study also investigated the developmental changes in expression of membrane proteins in neonate and child monkeys. Expression of MDR1 was similar in neonate and adult monkeys, whereas in rat, P-glycoprotein expression was reported to be significantly lower in brain microvessels of neonate as compared with adult rat. These results will be helpful to understand and predict brain concentrations of drugs in different species and at different ages of primates.
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PMID:Quantitative membrane protein expression at the blood-brain barrier of adult and younger cynomolgus monkeys. 2125 69