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Originally published as JHC exPRESS on June 26, 2006.
doi:10.1369/jhc.5A6870.2006
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Journal of Histochemistry and Cytochemistry
Volume 54 (10): 1159-1167, 2006
Copyright ©The Histochemical Society, Inc.

In Situ Localization of P-glycoprotein (ABCB1) in Human and Rat Brain

Reina Bendayan, Patrick T. Ronaldson, Diane Gingras and Moise Bendayan

Department of Pharmaceutical Sciences, Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, Canada (RB,PTR), and Department of Pathology and Cell Biology, Faculty of Medicine, University of Montreal, Montreal, Canada (DG,MB)

Correspondence to: Dr. Moise Bendayan, Department of Pathology and Cell Biology, Faculty of Medicine, University of Montreal, CP 6128 Succursale Centre-ville, Montreal, PQ, Canada H3T 1J4. E-mail: moise.bendayan{at}umontreal.ca

Transport of several xenobiotics including pharmacological agents into or out of the central nervous system (CNS) involves the expression of ATP-dependent, membrane-bound efflux transport proteins such as P-glycoprotein (P-gp) at the blood–brain barrier (BBB). Previous studies have documented gene and protein expression of P-gp in brain microvessel endothelial cells. However, the exact localization of P-gp, particularly at the abluminal side of the BBB, remains controversial. In the present study we examined the cellular/subcellular distribution of P-gp in situ in rat and human brain tissues using immunogold cytochemistry at the electron microscope level. P-gp localizes to both the luminal and abluminal membranes of capillary endothelial cells as well as to adjacent pericytes and astrocytes. Subcellularly, P-gp is distributed along the nuclear envelope, in caveolae, cytoplasmic vesicles, Golgi complex, and rough endoplasmic reticulum (RER). These results provide evidence for the expression of P-gp in human and rodent brain capillary along their plasma membranes as well as at sites of protein synthesis, glycosylation, and membrane trafficking. In addition, its presence at the luminal and abluminal poles of the BBB, including pericytes and astrocyte plasma membranes, suggests that this glycoprotein may regulate drug transport processes in the entire CNS BBB at both the cellular and subcellular level. (J Histochem Cytochem 54:1159–1167, 2006)

Key Words: P-glycoprotein • brain capillary endothelial cell • immunogold cytochemistry • luminal plasma membrane • abluminal plasma membrane • blood–brain barrier


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