Mrp1 Multidrug Resistance-Associated Protein and P-Glycoprotein Expression in Rat Brain Microvessel Endothelial Cells

Autor: Anthony Regina, Ahmet Koman, Michèle Piciotti, Bouchra El Hafny, Melvin S. Center, Ralf Bergmann, Pierre-Olivier Couraud, Françoise Roux
Rok vydání: 2002
Předmět:
Pathology
medicine.medical_specialty
Endothelium
Immunoblotting
Vinblastine
Blood–brain barrier
Polymerase Chain Reaction
Biochemistry
Gout Suppressants
Rats
Sprague-Dawley
Cellular and Molecular Neuroscience
Benzbromarone
Parenchyma
medicine
Animals
Cytotoxic T cell
ATP Binding Cassette Transporter
Subfamily B
Member 1
RNA
Messenger
Enzyme Inhibitors
Microvessel
Cell Line
Transformed
P-glycoprotein
biology
Probenecid
Brain
Uricosuric Agents
Sulfinpyrazone
Antineoplastic Agents
Phytogenic
Genistein
Capillaries
Rats
Cell biology
DNA-Binding Proteins
Gene Expression Regulation
Neoplastic
Endothelial stem cell
medicine.anatomical_structure
Vincristine
Cell culture
Astrocytes
MutS Homolog 3 Protein
Carcinogens
Cyclosporine
biology.protein
Endothelium
Vascular
Multidrug Resistance-Associated Proteins
Colchicine
Zdroj: Journal of Neurochemistry, Vol. 71, No. 2, 1998, 705-715
ISSN: 1471-4159
0022-3042
Popis: Two membrane glycoproteins acting as energy-dependent efflux pumps, mdr-encoded P-glycoprotein (P-gp) and the more recently described multidrug resistance-associated protein (MRP), are known to confer cellular resistance to many cytotoxic hydrophobic drugs. In the brain, P-gp has been shown to be expressed specifically in the capillary endothelial cells forming the blood-brain barrier, but localization of MRP has not been well characterized yet. Using RT-PCR and immunoblot analysis, we have compared the expression of P-gp and Mrp1 in homogenates, isolated capillaries, primary cultured endothelial cells, and RBE4 immortalized endothelial cells from rat brain. Whereas the mdr1a P-gp-encoding mRNA was specifically detected in brain microvessels and mdr1b mRNA in brain parenchyma, mrp1 mRNA was present both in microvessels and in parenchyma. However, Mrp1 was weakly expressed in microvessels. Mrp1 expression was higher in brain parenchyma, as well as in primary cultured brain endothelial cells and in immortalized RBE4 cells. This Mrp1 overexpression in cultured brain endothelial cells was less pronounced when the cells were cocultured with astrocytes. A low Mrp activity could be demonstrated in the endothelial cell primary monocultures, because the intracellular [3H]vincristine accumulation was increased by several MRP modulators. No Mrp activity was found in the cocultures or in the RBE4 cells. We suggest that in rat brain, Mrp1, unlike P-gp, is not predominantly expressed in the blood-brain barrier endothelial cells and that Mrp1 and the mdr1b P-gp isoform may be present in other cerebral cells.
Databáze: OpenAIRE
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