Functional Evidence for P-glycoprotein at the Nose-Brain Barrier
| Autor: | Candace L. Graff, Gary M. Pollack |
|---|---|
| Rok vydání: | 2005 |
| Předmět: |
Pathology
medicine.medical_specialty Pharmacology toxicology Pharmaceutical Science Nose Blood–brain barrier Mice otorhinolaryngologic diseases medicine Animals Distribution (pharmacology) Pharmacology (medical) ATP Binding Cassette Transporter Subfamily B Member 1 Anatomic Location Administration Intranasal P-glycoprotein Pharmacology Dose-Response Relationship Drug biology business.industry Organic Chemistry Brain medicine.anatomical_structure Anesthesia biology.protein Molecular Medicine Nasal Cavity Rifampin business Biotechnology |
| Zdroj: | Pharmaceutical Research. 22:86-93 |
| ISSN: | 1573-904X 0724-8741 |
| DOI: | 10.1007/s11095-004-9013-3 |
| Popis: | Experiments were performed to assess the brain distribution of [3H]-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. [3H]-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 [3H]-verapamil, regardless of delivery route (Imax = 62 +/- 6%). The ED50 for enhancement of [3H]-verapamil uptake by nasal rifampin was approximately 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 [3H]-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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full text from SpringerLink