High levels of P-glycoprotein detected in isolated brain capillaries

Jetté, Lucie; Têtu, Bernard; Béliveau, Richard

doi:10.1016/0005-2736(93)90083-c

Cited by 106 publications

(47 citation statements)

References 26 publications

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“…multidrug resistant (MDR) [1]. This protein is also present in a number of normal tissues including vascular endothelial cells lining the capillaries that form part of the blood-brain barrier [2,3,4]. Recent evidence suggests that it may be important in this situation for preventing entry of toxic substances to the brain [5].…”

Section: Introductionmentioning

confidence: 99%

Comparisons of P‐glycoprotein expression in isolated rat brain microvessels and in primary cultures of endothelial cells derived from microvasculature of rat brain, epididymal fat pad and from aorta

1995

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In vivo expression of P-glycoprotein in isolated rat brain mierovessels is compared with that in vitro in primary cultures of brain endothelial cells. More P-glycoprotein is detected by Western immunoblotting in microvessels than in cultured endothelium. RT-PCR with isnform-specific primers and immunobiotting with a mdrlb-specific antibody reveals only mdrla in vivo but both mdrla and mdrlb in vitro. Thus mdrla decreases whereas mdrlb increases during culture. P-Glycoprotein activity is evident in vitro, with resistance modulators, e.g. verapamil, producing increases in intracenular [3H]vincristine accumulation. Endothelial cells cultured from epididymal fat pad microvaseulature and aorta contain little or no P-glycoprotein. Here, resistance modulators are less effective.

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Section: Introductionmentioning

confidence: 99%

Comparisons of P‐glycoprotein expression in isolated rat brain microvessels and in primary cultures of endothelial cells derived from microvasculature of rat brain, epididymal fat pad and from aorta

1995

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“…On the contrary, in the BBB microvessels, where the highest levels of P-gp have been detected, the transporter was described only at the luminal endothelial membrane. This selective one-front localization suggests that P-gp plays a barrier protective role by extruding cytotoxic substances and drugs from the endothelial cells back into the bloodstream (Jetté et al 1993;Stewart et al 1996;Beaulieu et al 1997;Demeule et al 2001). This P-gp defense activity is likely to acquire great relevance in human brain, in which the levels of P-gp are three-to fivefold higher than in murine and bovine brain (Jetté et al 1993).…”

mentioning

confidence: 99%

“…This selective one-front localization suggests that P-gp plays a barrier protective role by extruding cytotoxic substances and drugs from the endothelial cells back into the bloodstream (Jetté et al 1993;Stewart et al 1996;Beaulieu et al 1997;Demeule et al 2001). This P-gp defense activity is likely to acquire great relevance in human brain, in which the levels of P-gp are three-to fivefold higher than in murine and bovine brain (Jetté et al 1993). Despite the volume of data available on P-gp, some aspects, such as the cellular site of expression and regulation of its activity, have not yet been clarified.…”

mentioning

confidence: 99%

Expression of P-Glycoprotein in Human Cerebral Cortex Microvessels

Virgintino

Robertson

Errede

et al. 2002

J Histochem Cytochem.

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S U M M A R Y P-Glycoprotein (P-gp) is an ATP-dependent efflux transporter that extrudes non-polar molecules, including cytotoxic substances and drugs, from the cells. It was initially found in cancer cells and then was shown to be a normal component of complex transport systems working at the blood-brain barrier (BBB). Previous studies have demonstrated that, in the brain, P-gp is localized on the luminal plasmalemma of BBB endothelial cells and that it may interact with the caveolar compartment of these cells. The aim of this study was to identify the site of cellular expression of P-gp in human brain in situ and to morphologically determine whether an association may exist between P-gp and caveolin-1, a structural and functional protein of the caveolar frame. The study was carried out on human cerebral cortex by immunoconfocal microscopy with antibodies to both P-gp and caveolin-1. The results show that P-gp marks the microvessels of the cortex and that the transporter is localized in the luminal endothelial compartment, where it co-localizes with caveolin-1. The demonstration of this co-localization of P-gp with caveolin-1 contributes a morphological backing to biochemical studies on P-gp/caveolin-1 relationships and leads us to suggest that interactions between these molecules may occur at the BBB endothelia.

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“…We have selected C219 as one of the antibodies, because it is one of the most widely used antibody for P-gp immunodetection in both research and diagnosis [20,21]. It recognizes amino acid sequence VQEALD of the cytoplasmic region of the protein, which is conserved in all cytosolic domains of P-gp from rodents to human [20,22,23]. H-241, a polyclonal antibody that recognizes amino acids 1040-1280 at the P-gp C-terminal cytoplasmic domain of human, mouse and rat origin was another antibody selected for this study.…”

Section: Resultsmentioning

confidence: 99%