Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
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Drug
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Query: EC:3.6.3.44 (
P-glycoprotein
)
13,344
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
To investigate the transport function of the blood-brain barrier (BBB), we employed an in vitro model of the BBB, consisting of a co-culture of porcine brain capillary endothelial cells (BCECs) with rat astrocytes. Porcine BCECs were cultured on a filter insert with rat astrocytes on the underlying plastic well. Rat astrocytes induced characteristic BBB properties of porcine BCECs, such as gamma-glutamyl-transpeptidase activity and intercellular adhesion of porcine BCECs. Next, the transport properties of
P-glycoprotein
(
P-gp
) substrate and several anionic compounds across the co-cultured porcine BCECs were characterized. Expression of
P-gp
was detected by immunocytochemistry, and efflux-directed transport of the
P-gp
substrate [(3)H]daunomycin was observed. Luminal-to-abluminal transport of the
monocarboxylic acid transporter 1
(
MCT1
) substrate [(14)C]benzoic acid was saturable, and the K(m) value (3.05 mM) was similar to that for brain uptake observed in vivo. Abluminal-to-luminal transport of [(14)C]benzoic acid was also saturable, indicating that the monocarboxylic acid transporter of the BBB contributes to the efflux from the brain as well as to blood-to-brain influx. Abluminal-to-luminal transport of organic anions, [(3)H]dehydroepiandrosterone sulfate, [(3)H]estrone sulfate and [(3)H]estradiol 17beta-D-glucuronide was significantly higher than the corresponding luminal-to-abluminal transport. These results demonstrate the presence of multiple efflux transport pathways in this in vitro model.
...
PMID:Evaluation of blood-brain barrier transporters by co-culture of brain capillary endothelial cells with astrocytes. 1561 50
An in vitro cell culture system for estimating the human blood-brain barrier (BBB) permeability of drugs is required for the development of drugs with effects on the central nervous system. In this study, cultured human brain microvascular endothelial cells (hBME) were characterized. hBME cells exhibited concentration-dependent uptake of L-Leu, L-Glu and L-Lys with K(m) values of 51.1+/-23.1 microM, 163.3+/-79.8 microM and 72.4+/-56.6 microM, respectively. The cellular accumulation of rhodamine123 in hBME cells was unaffected by
P-glycoprotein
(
P-gp
) substrates (cyclosporin A, quinidine and verapamil), while the accumulation in human
P-gp
-overexpressing cells was significantly increased in the presence of these
P-gp
substrates. RT-PCR revealed that hBME cells expressed large neutral amino acid transporter 1 (LAT1) and its associated molecule (4F2hc), excitatory amino acid transporter 3 (EAAT3), cationic amino acid transporter 1 (CAT1), glucose transporter 1 (GLUT1),
monocarboxylic acid transporter 1
(
MCT1
) and multidrug resistance-associated protein 1 (MRP1). However, no expression of multidrug resistance protein 1 (MDR1) was detected. The results suggest that these amino acid transporters are functionally expressed at the human BBB, and that hBME cells retain the in vivo BBB transport functions and expression characteristics. Consequently, hBME cells should be a useful tool for studies of the human BBB.
...
PMID:mRNA expression and amino acid transport characteristics of cultured human brain microvascular endothelial cells (hBME). 1561 88
