Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
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Drug
Enzyme
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Target Concepts:
Gene/Protein
Disease
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Enzyme
Compound
Query: EC:3.6.3.44 (
P-glycoprotein
)
13,344
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Overexpression of human MDR1
P-glycoprotein
[Pgp] is associated with cellular resistance to bulky amphipathic drugs, such as taxol, anthracyclines, vinca alkaloids, and epipodophyllotoxins by actively effluxing drugs from cells. We have found that human MDR1 transfected murine L1210/VMDRC.06 leukemia cells exhibit relatively large amounts of Pgp and high levels of resistance to 6-mercaptopurine [
6-MP
] and other purine and pyrimidine nucleobase and nucleoside analogs. L1210/VMDRC.06 cells accumulated
6-MP
as the nucleotide in vitro at only about one-third of that formed by parental L1210 cells in normal medium; however, under conditions of ATP-depletion, the amount of
6-MP
nucleotide formed was essentially the same in both cell lines. The findings support active efflux of
6-MP
in L1210 cells, suggesting involvement of Pgp in
6-MP
resistance even though it is generally believed that Pgp does not transport such agents. The resistance pattern observed in L1210/VMDRC.06 cells was not duplicated in P388/VMDRC.04 leukemia cells transfected with the same MDR1 cDNA, even though a similar amount of Pgp was present in both cell lines. Immunofluorescent staining of surface membrane Pgp showed that L1210/VMDRC.06 cells contained at least three-fold more surface Pgp than P388/VMDRC.04, implying that P388/VMDRC.04 cells are unable to actively efflux
6-MP
and other antimetabolites as effectively as L1210/VMDRC.06, because of significantly lower membrane Pgp. The findings suggest that the exceedingly large concentration of overexpressed Pgp in the surface membrane of L1210/MDRC.06 cells is responsible for resistance to
6-MP
and other purine and pyrimidine analogs, even though these agents usually are not considered to be substrates for Pgp.
...
PMID:Resistance to purine and pyrimidine nucleoside and nucleobase analogs by the human MDR1 transfected murine leukemia cell line L1210/VMDRC.06. 1529 54
The purpose of the present study was to characterize rat organic anion transporter (Oat) 3 (Oat3, Slc22a8) in the efflux transport at the inner blood-retinal barrier (BRB). Reverse transcription-polymerase chain reaction analysis showed that rat (r) Oat3 mRNA is expressed in retinal vascular endothelial cells (RVECs), but not rOat1 and rOat2 mRNA. The expression of Oat3 in the retina and human cultured retinal endothelial cells was further confirmed by Western blot analysis. Immunohistochemical staining in RVECs showed that rOat3 is colocalized with glucose transporter 1, but not
P-glycoprotein
, suggesting that rOat3 is possibly located at the abluminal membrane of the RVEC. The contribution of rOat3 to the efflux of [(3)H]p-aminohippuric acid ([(3)H]PAH), [(3)H]benzylpenicillin ([(3)H]PCG), and [(14)C]6-mercaptopurine ([(14)C]
6-MP
), substrates of rOat3, from the vitreous humor/retina to the circulating blood across the inner BRB was evaluated using the microdialysis method. [(3)H]PAH, [(3)H]PCG, [(14)C]
6-MP
, and [(14)C] or [(3)H]d-mannitol, a bulk flow marker, were biexponentially eliminated from the vitreous humor after vitreous bolus injection. The elimination rate constant of [(3)H]PAH, [(3)H]PCG, and [(14)C]
6-MP
during the terminal phase was approximately 2-fold greater than that of d-mannitol. This efflux transport was reduced in the retinal presence of probenecid, PAH, and PCG, whereas it was not inhibited by digoxin. In conclusion, rOat3 is expressed at the inner BRB and involved in the vitreous humor/retina-to-blood transport of PAH, PCG, and
6-MP
. This transport system is one mechanism to limit the retinal distribution of PAH, PCG, and
6-MP
.
...
PMID:Roles of inner blood-retinal barrier organic anion transporter 3 in the vitreous/retina-to-blood efflux transport of p-aminohippuric acid, benzylpenicillin, and 6-mercaptopurine. 1911 70
Ulcerative colitis (UC) is characterized by a long-standing chronic course with remissions and exacerbations. Previously, patients do not respond to 5-aminosalicylic acid compounds and corticosteroids are considered for colectomies, however, in recent years, alternative treatments emerged for steroid-refractory or steroid-dependent UC. In this review article, we focus on immunomodulators (such as azathioprine [AZA] and 6-mercaptopurine [
6-MP
]) and immunosuppressants (such as cyclosporine A [CSA] and tacrolimus [FK506]) for steroid-refractory or steroid-dependent ulcerative colitis. The characteristics, efficacy and adverse effects of these drugs are outlined. Although the randomized trial of FK506 is conducted in Japan, the clinical data of CSA in Japanese patients are limited. The short-, mid- and long-term follow-ups of CSA administration in Japanese patients are discussed. As for thipurine drugs, the clinical importance of
multidrug-resistance protein
4 (MRP4) in Japanese patients is highlighted.
...
PMID:Immunomodulators and immunosuppressants for Japanese patients with ulcerative colitis. 2199 97
