NDLI: Functional Evidence for P-glycoprotein at the Nose-Brain Barrier

Content Provider	Springer Nature Link
Author	Graff, Candace L. Pollack, Gary M.
Copyright Year	2005
Abstract	Experiments were performed to assess the brain distribution of [$^{3}$H]-verapamil, including the influence of delivery route of inhibitor and substrate (nasal vs. systemic) on brain distribution. The anatomic location of P-glycoprotein (P-gp) at the nose-brain barrier also was investigated.Separate groups of mice were pretreated with rifampin or vehicle nasally or intravenously. [$^{3}$H]-verapamil was administered either nasally or via in situ brain perfusion, and dose-response profiles were constructed for P-gp inhibition. Localization of P-gp in freshly obtained brain slices and olfactory tissue was evaluated by confocal microscopy.Rifampin inhibited the P-gp–mediated efflux of [$^{3}$H]-verapamil, regardless of delivery route (I$_{max}$ = 62 ± 6%). The ED$_{50}$ for enhancement of [$^{3}$H]-verapamil uptake by nasal rifampin was ∼400-fold lower than for intravenous rifampin (0.16 vs. 65 mg/kg, respectively). Microscopy showed that P-gp was located in endothelial cells that line the olfactory bulb and within the olfactory epithelium.Nasal delivery of rifampin enhanced brain uptake of [$^{3}$H]-verapamil. The magnitude of transport inhibition was dependent on the dose and route of the inhibitor, the time after administration of the inhibitor, and the specific brain region examined. P-gp is localized to both the olfactory epithelium and the endothelial cells that surround the olfactory bulb.
Starting Page	86
Ending Page	93
Page Count	8
File Format	PDF
ISSN	07248741
Journal	Pharmaceutical Research
Volume Number	22
Issue Number	1
e-ISSN	1573904X
Language	English
Publisher	Kluwer Academic Publishers-Plenum Publishers
Publisher Date	2005-01-01
Publisher Place	New York
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	brain slices blood-brain barrier nasal delivery P-glycoprotein pharmacokinetics Pharmacology/Toxicology Pharmacy Biochemistry Medical Law Biomedical Engineering
Content Type	Text
Resource Type	Article
Subject	Organic Chemistry Pharmacology Molecular Medicine Pharmacology (medical) Biotechnology Pharmaceutical Science

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