Regulation by cannabinoid receptors of anandamide transport across the blood-brain barrier and through other endothelial cells

Mauro Maccarrone, Anna Fiori, Monica Bari, Filippo Granata, Valeria Gasperi, M. Egle De Stefano, Alessandro Finazzi-Agrò, Roberto Strom

Research output: Contribution to journalArticle

Abstract

The endocannabinoid anandamide (AEA) has many neurovascular activities. However, it is not yet clear how AEA can be metabolized at the neurovascular interface, and how it can move through the vascular and the cerebral compartments. The results reported in this article show that isolated bovine brain microvessels, an ex vivo model of the blood-brain barrier, have detectable levels of endogenous AEA and possess the biochemical machinery to bind and metabolize it, i.e. type-1 and type-2 cannabinoid receptors (CB1R and CB2R), a selective AEA membrane transporter (AMT), an AEA-degrading fatty acid amide hydrolase, and the AEA-synthesizing enzymes N-acyltransferase and N-acyl-phosphatidylethanolamines-specific phospholipase D. We also show that activation of CB1R enhances AMT activity through increased nitric oxide synthase (NOS) activity and subsequent increase of NO production.AMT activity is instead reduced by activation of CB2R, which inhibits NOS and NO release. In addition, binding experiments and immunoelectron-microscopy demonstrate that different endothelial cells vary in the expression of CB1R and CB2R on the luminal and/or abluminal sides. The different localization of CBRs can lead to a diverse effect on AMT activity on the luminal and abluminal membranes, suggesting that the distribution of these receptors may drive AEA directional transport through the blood-brain barrier and other endothelial cells.

Original languageEnglish
Pages (from-to)117-127
Number of pages11
JournalThrombosis and Haemostasis
Volume95
Issue number1
DOIs
Publication statusPublished - Jan 2006

Keywords

  • Brain
  • Directional uptake
  • Endocannabinoids
  • Endothelial cells
  • Nitric oxide
  • Receptors
  • Transporters

ASJC Scopus subject areas

  • Hematology

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