Immunohistochemical localization in normal tissues of different epitopes in the multidrug transport protein P170: evidence for localization in brain capillaries and crossreactivity of one antibody with a muscle protein.

Thiébaut, F; Tsuruo, Takashi; Hamada, Hirofumi; Gottesman, Michael M.; Pastan, Ira; Willingham, Mark C.

doi:10.1177/37.2.2463300

Cited by 556 publications

(253 citation statements)

References 23 publications

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“…The transporting P-gps are generally overexpressed in tumor cells, conferring resistance against cytotoxic agents and are associated with specialized normal tissue barriers (e.g., blood-brain barrier, blood-testis barrier, blood-ovarian barrier, placenta, gastrointestinal epithelium, etc.) [6][7][8].…”

Section: Discussionmentioning

confidence: 99%

“…Most of the substrates for P-gp are toxic compounds of natural or semisynthetic origin [5]. P-gp is expressed in various normal human tissues, such as small intestine, kidney, liver, and capillary endothelial cells of brain and testes [6][7][8]. Based on the tissue distribution, P-gp has been proposed to have a significant role in the protection of organisms against toxic xenobitics [9,10].…”

Section: Introductionmentioning

confidence: 99%

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Functional expression of P-glycoprotein in primary cultures of human cytotrophoblasts and BeWo cells☆

Utoguchi

Chandorkar

Avery

et al. 2000

Reproductive Toxicology

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Functional expression of P-glycoprotein in primary cultures of human cytotrophoblasts and BeWo cells☆

Utoguchi

Chandorkar

Avery

et al. 2000

Reproductive Toxicology

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“…MDR1-type P-glycoprotein has been found in the apical membrane of the intestinal epithelial cells (Mukhopadhyay et al 1988), in the biliary canalicular membrane of hepatocytes, and in the lumenal membrane of proximal tubular epithelial cells in the kidney (Thiebaut et al 1987(Thiebaut et al , 1989. High levels of MDR1 P-glycoprotein have been found in the lumenal membrane of the endothelial cells that line small blood capillaries and form the blood-brain and blood-testis barrier (Thiebaut et al 1989;Cordon-Cardo et al 1989Tsuji et al 1992).…”

Section: Mice With a Genetic Disruption (Knockout) Of The Multiple Drmentioning

confidence: 99%

“…High levels of MDR1 P-glycoprotein have been found in the lumenal membrane of the endothelial cells that line small blood capillaries and form the blood-brain and blood-testis barrier (Thiebaut et al 1989;Cordon-Cardo et al 1989Tsuji et al 1992). In addition, it has been demonstrated that P-glycoprotein found in the blood-brain barrier limits the brain accumulation of many drugs (Schinkel 1995a).…”

Section: Mice With a Genetic Disruption (Knockout) Of The Multiple Drmentioning

confidence: 99%

Penetration of Amitriptyline, but Not of Fluoxetine, into Brain is Enhanced in Mice with Blood-Brain Barrier Deficiency Due to Mdr1a P-Glycoprotein Gene Disruption

Uhr

Steckler

Yassouridis

et al. 2000

Neuropsychopharmacology

215

152

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Mice with a genetic disruption (knockout) of the multiple drug resistance (Mdr1a) gene were used to examine the effect of the absence of the drug-transporting P-glycoproteinat the blood-brain barrier on the uptake of amitriptyline (AMI) and fluoxetine (FLU) P-glycoprotein is encoded by the MDR1 gene in humans and the mdr1a (also called mdr3) and mdr1b (also called mdr1) gene in mice (Devault and Gros 1990). Although mdr1a and mdr1b are not always expressed in the same organs, the overall distribution of these genes in mice tissue coincides roughly with that of the single MDR1 gene in humans, suggesting that mdr1a and From the

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“…Pgp is a drug e ux pump that is present on the luminal surface of brain capillary endothelial cells [3,4]. It appears to play an important role in excluding xenobiotics, including a variety of anticancer drugs, from the CNS [5±8].…”

Section: Introductionmentioning

confidence: 99%

Effect of P-glycoprotein modulation with cyclosporin A on cerebrospinal fluid penetration of doxorubicin in non-human primates

Warren

Patel

McCully

et al. 2000

Cancer Chemotherapy and Pharmacology

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Purpose: P-glycoprotein (Pgp) is a transmembrane drug e ux pump that is expressed in multidrugresistant cancer cells and in a variety of normal tissues, including brain capillary endothelial cells which comprise the blood-brain barrier. We studied the e ects of the Pgp inhibitor, cyclosporin A (CsA), on the cerebrospinal¯uid (CSF) penetration of the Pgp substrate, doxorubicin, in non-human primates. Methods: The animals received doxorubicin alone (2.0 mg/kg i.v. over 60 min) or doxorubicin (1 mg/kg i.v. over 60 min) and CsA (loading dose 4.0 mg/kg i.v. over 2 h, followed by continuous infusion of 12 mg/kg per day over 48 h). Plasma and CSF were collected over 48 h and the doxorubicin concentration was measured by reverse-phase high-pressure liquid chromatography (HPLC) with uorescence detection (detection limit 5 nM). A twocompartment model was ®tted to the plasma concentration-time data. Results: Pgp was demonstrated to be present in the epithelium of the choroid plexus by immunohistochemical methods, indicating that CSF drug penetration could be used as a surrogate for bloodbrain barrier penetration. Steady state whole blood CsA concentrations, which were measured with a¯uores-cence-polarization immunoassay (TDX) that detects both CsA and its metabolites, ranged from 551±1315 lg/ l at 24 h. The clearance of doxorubicin in four animals was reduced by 34%, 38%, 45% and 49% when given with CsA.

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Immunohistochemical localization in normal tissues of different epitopes in the multidrug transport protein P170: evidence for localization in brain capillaries and crossreactivity of one antibody with a muscle protein.

Abstract: MAb C219 showed intense localization in selected skeletal muscle fibers and all cardiac muscle fibers in rat and human tissues. ATPase cytochemistry showed

Cited by 556 publications

References 23 publications

Functional expression of P-glycoprotein in primary cultures of human cytotrophoblasts and BeWo cells☆

Functional expression of P-glycoprotein in primary cultures of human cytotrophoblasts and BeWo cells☆

Penetration of Amitriptyline, but Not of Fluoxetine, into Brain is Enhanced in Mice with Blood-Brain Barrier Deficiency Due to Mdr1a P-Glycoprotein Gene Disruption

Effect of P-glycoprotein modulation with cyclosporin A on cerebrospinal fluid penetration of doxorubicin in non-human primates

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