Uptake of drugs and expression of P-glycoprotein in the rat 9L glioma.

Uptake of drugs and expression of P-glycoprotein in the rat 9L glioma. Research Abstract Details 

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Uptake of drugs and expression of P-glycoprotein in the rat 9L glioma. Abstract Text:

T Yamashima,T Ohnishi,Y Nakajima,T Terasaki,M Tanaka,J Yamashita,T Sasaki,A Tsuji,

Two weeks after the inoculation of 1.5 x 10(5) 9L glioma cells into the rat brain, the uptake of radiolabelled drugs into the brain and the experimental 9L glioma during the first cerebral circulation was measured with a liquid scintillation counter and analyzed by the method of Oldendorf (1970). The expression of P-glycoprotein, which is known to be associated with the efflux of drugs, was also studied, using anti-P-glycoprotein monoclonal antibody, C-219. Furthermore, the ultrastructure of brain capillaries, tumor vessels, and glioma cells was studied by conventional and immunoelectron microscopy. Sucrose (control), the transport of which through the blood-brain barrier is known to be negligible, accumulated to fivefold higher levels in the tumor than in normal brain. Ranimustine (MCNU), 5-fluorouracil (5-FU), and doxorubicin showed little accumulation in the normal brain, whereas nimustine (ACNU) showed an increased accumulation. MCNU and doxorubicin showed negligible accumulation in the glioma cells despite diffusion into the tumor interstitial space. In contrast, ACNU and 5-FU showed an increased accumulation in tumor cells. The accumulation of 5-FU in the cultured 9L glioma cells was decreased by ATP inhibitors or by low temperature. Although both brain capillary endothelial cells and glioma cell membrane were immunohistochemically positive for P-glycoprotein, the tumor vasculature showed low expression of P-glycoprotein. The endothelial cells of tumor vessels ultrastructurally showed increased fenestrations, swelling, and disrupted junctions. Accordingly, it is suggested that hydrophobic drugs such as doxorubicin, being pumped out by P-glycoprotein, do not accumulate in 9L glioma cells as do other lipophilic drugs such as ACNU, or drugs such as 5-FU, which accumulate by a carrier-mediated mechanism.

Uptake of drugs and expression of P-glycoprotein in the rat 9L glioma. Publishing Authors By Initials

T Yamashima,T Ohnishi,Y Nakajima,T Terasaki,M Tanaka,J Yamashita,T Sasaki,A Tsuji,

For similar cardiovascular system: blood vessels: microcirculation: venules research abstracts see: cardiovascular system: blood vessels: microcirculation: venules research

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Uptake of drugs and expression of P-glycoprotein in the rat 9L glioma. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Experimental brain research. Experimentelle Hirnfo

VOLUME: 95

Page Numbers: 41-50

Journal Abbreviation:

ISSN: 0014-4819

DAY: 15

MONTH: 02

YEAR: 1993

Uptake of drugs and expression of P-glycoprotein in the rat 9L glioma. Information

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LANGUAGE: eng

NlmUniqueID: 43312

Uptake of drugs and expression of P-glycoprotein in the rat 9L glioma. Keywords Mesh Terms:

KEYWORDS: Venules

MESH TERMS: ultrastructure

Chemical & Substance for Abstract: Uptake of drugs and expression of P-glycoprotein in the rat 9L glioma. Information

Substance Name: Sucrose

Registry Number: 57-50-1

Grant and Affiliation Information for Uptake of drugs and expression of P-glycoprotein in the rat 9L glioma.

AFFILIATION: Department of Neurosurgery, School of Medicine, Kanazawa University, Japan.

Country: GERMANY

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MEDLINETA: Exp Brain Res

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