A previous study demonstrated that only a portion of P-gp molecules [11] are associated with caveolin-1, which suggests that different cell
phenotypes may modify the localization of P-gp and caveolin-1, and different cellular events may lead to redistribution of both proteins. In summary, the present study indicates that P-gp is mainly expressed in capillary endothelial cells and end-feet of glial cells. P-gp, an important part of the blood brain barrier, plays a Bafilomycin A1 significant role in brain tumor resistance. In addition, the expression of P-gp in the interstitial cells was related to the distance of the cells from the capillary Selleckchem CDK inhibitor wall. The nearer the cell was to the capillary wall, the stronger the expression of P-gp. In the brain, the expression of P-gp and caveolin-1 was found at both the end-feet of astrocytes and microvascular endothelium. The parallel expression of P-gp and caveolin-1 supports the hypothesis that these two transporter proteins may work in concert to mediate transport processes in the brain at several levels, including the microvascular endothelium, the microvascular astrocytic end-feet, and parenchymal astrocytic processes. Acknowledgements This research
was supported by the National GS-7977 Natural Science Foundation of China (No. 30600579). References 1. Sun H, Dai H, Shaik N, Elmquist WF: Drug efflux transporters in the CNS. Adv Drug Deliv Rev 2003, 55:83–105.PubMedCrossRef 2. Linnet K, Ejsing TB: A review on the impact
of P-glycoprotein on the penetration of drugs into the brain. Focus on psychotropic drugs. Eur Neuropsychopharmacol 2008,18(3):157–169.PubMedCrossRef 3. Bart J, Groen HJ, Hendrikse NH, van der Graaf WT, Vaalburg W, de Vries EG: The blood-brain barrier and oncology: new insights into function and modulation. Cancer Treat Rev 2000, 26:449–462.PubMedCrossRef 4. Demeule M, Régina A, Jodoin J, Laplante A, Dagenais C, Berthelet F, Moghrabi A, Béliveau R: Drug transport to the brain:Key roles for the efflux pump P-glycoprotein in the blood-brain barrier. Vascular Pharmacology 2002, 38:339–348.PubMedCrossRef 5. Choong E, Dobrinas M, Carrupt PA, Eap CB: The permeability Montelukast Sodium P-glycoprotein: a focus on enantioselectivity and brain distribution. Expert Opin Drug Metab Toxicol 2010,6(8):953–65.PubMedCrossRef 6. Chen C, Liu X, Smith BJ: Utility of mdr1-gene deficient mice in assessing the impact of P-glycoprotein on the pharmacokinetics and pharmacodynamics in drug discovery and development. Curr Drug Metab 2003, 4:272–291.PubMedCrossRef 7. Sun J, He ZG, Cheng G, Wang SJ, Hao XH, Zou MJ: Multidrug resistance P-glycoprotein: crucial significance in drug disposition and interaction. Med Sci Monit 2004,10(1):RA5–14.PubMed 8. Demeule M, Labelle M, Régina A, Berthelet F, Béliveau R: Isolation of endothelial cell from brain, lung, and kidney: expression of the multidrug resistance P-glycoprotein isoforms. Biochem Biophys Res Commun 2001, 281:827–834.