In situ localization of P-glycoprotein (ABCB1) in human and rat brain

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

Research output: Contribution to journalArticle

155 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1159-1167
Number of pages9
JournalJournal of Histochemistry and Cytochemistry
Volume54
Issue number10
DOIs
StatePublished - Oct 2006
Externally publishedYes

Fingerprint

P-Glycoprotein
Blood-Brain Barrier
Brain
Pericytes
Astrocytes
Membranes
Central Nervous System
Endothelial Cells
Cell Membrane
Cytoplasmic Vesicles
Caveolae
Histocytochemistry
Rough Endoplasmic Reticulum
Membrane Glycoproteins
Nuclear Envelope
Golgi Apparatus
Xenobiotics
Microvessels
Glycosylation
Rodentia

Keywords

  • Abluminal plasma membrane
  • Blood-brain barrier
  • Brain capillary endothelial cell
  • Immunogold cytochemistry
  • Luminal plasma membrane
  • P-glycoprotein

ASJC Scopus subject areas

  • Anatomy
  • Cell Biology

Cite this

In situ localization of P-glycoprotein (ABCB1) in human and rat brain. / Bendayan, Reina; Ronaldson, Patrick T; Gingras, Diane; Bendayan, Moise.

In: Journal of Histochemistry and Cytochemistry, Vol. 54, No. 10, 10.2006, p. 1159-1167.

Research output: Contribution to journalArticle

Bendayan, Reina ; Ronaldson, Patrick T ; Gingras, Diane ; Bendayan, Moise. / In situ localization of P-glycoprotein (ABCB1) in human and rat brain. In: Journal of Histochemistry and Cytochemistry. 2006 ; Vol. 54, No. 10. pp. 1159-1167.
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