Source:http://linkedlifedata.com/resource/pubmed/id/11356720
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
6
|
| pubmed:dateCreated |
2001-5-17
|
| pubmed:abstractText |
In the present study, we investigated the role of the multidrug resistance (mdr) P-glycoprotein (Pgp) at the blood-brain barrier in the control of access of cortisol and corticosterone to the mouse and human brain. [(3)H]Cortisol poorly penetrated the brain of adrenalectomized wild-type mice, but the uptake was 3.5-fold enhanced after disruption of Pgp expression in mdr 1a(-/-) mice. In sharp contrast, treatment with [(3)H]corticosterone revealed high labeling of brain tissue without difference between both genotypes. Interestingly, human MDR1 Pgp also differentially transported cortisol and corticosterone. LLC-PK1 monolayers stably transfected with MDR1 complementary DNA showed polar transport of [(3)H]cortisol that could be blocked by a specific Pgp blocker, whereas [(3)H]corticosterone transport did not differ between transfected and host cells. Determination of the concentration of both steroids in extracts of human postmortem brain tissue using liquid chromatography mass spectrometry revealed that the ratio of corticosterone over cortisol in the brain was significantly increased relative to plasma. In conclusion, the data demonstrate that in both mouse and human brain the penetration of cortisol is less than that of corticosterone. This finding suggests a more prominent role for corticosterone in control of human brain function than hitherto recognized.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
AIM
|
| pubmed:chemical | |
| pubmed:status |
MEDLINE
|
| pubmed:month |
Jun
|
| pubmed:issn |
0013-7227
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| pubmed:author | |
| pubmed:issnType |
Print
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| pubmed:volume |
142
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
2686-94
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| pubmed:dateRevised |
2006-11-15
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| pubmed:meshHeading |
pubmed-meshheading:11356720-Amygdala,
pubmed-meshheading:11356720-Animals,
pubmed-meshheading:11356720-Biological Transport,
pubmed-meshheading:11356720-Brain,
pubmed-meshheading:11356720-Cell Line,
pubmed-meshheading:11356720-Cerebellum,
pubmed-meshheading:11356720-Chromatography, Liquid,
pubmed-meshheading:11356720-Corticosterone,
pubmed-meshheading:11356720-Drug Resistance, Multiple,
pubmed-meshheading:11356720-Epithelium,
pubmed-meshheading:11356720-Gene Expression,
pubmed-meshheading:11356720-Hippocampus,
pubmed-meshheading:11356720-Humans,
pubmed-meshheading:11356720-Hydrocortisone,
pubmed-meshheading:11356720-Kidney,
pubmed-meshheading:11356720-Male,
pubmed-meshheading:11356720-Mass Spectrometry,
pubmed-meshheading:11356720-Mice,
pubmed-meshheading:11356720-P-Glycoprotein,
pubmed-meshheading:11356720-Swine,
pubmed-meshheading:11356720-Transfection,
pubmed-meshheading:11356720-Tritium
|
| pubmed:year |
2001
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| pubmed:articleTitle |
Multidrug resistance P-glycoprotein hampers the access of cortisol but not of corticosterone to mouse and human brain.
|
| pubmed:affiliation |
Divisions of Medical Pharmacology, Leiden/Amsterdam Center for Drug Research, Leiden University, The Netherlands. Karssen@LACDR.LeidenUniv.nl
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| pubmed:publicationType |
Journal Article,
Comparative Study
|