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

Reina Bendayan ¹, Patrick T. Ronaldson ¹, Diane Gingras ¹ and Moise Bendayan ^1*

¹ Department of Pharmaceutical Sciences, Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, Ontario, Canada (RB,PTR,MB), and Department of Pathology and Cell Biology, Faculty of Medicine, University of Montreal, Montreal, Quebec, Canada (DG)

^* To whom correspondence should be addressed. E-mail: moise.bendayan{at}umontreal.ca .

Submitted on November 4, 2005
Accepted on 15 June 2006

	Abstract

Transport of several xenobiotics including pharmacological agents into or out of the CNS involves the expression of ATP-dependent, membrane-bound efflux transport proteins, such as P-gp, at the 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 in adjacent pericytes and astrocytes. Subcellularly P-gp is distributed along the nuclear envelope, in caveolae, cytoplasmic vesicles, Golgi complex and 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 CNS at both the cellular and subcellular level.

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

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