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Thromb Haemost 2006; 95(01): 117-127
DOI: 10.1160/TH05-06-0413
Endothelium and Vascular Development
Schattauer GmbH

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

Mauro Maccarrone
1   Department of Biomedical Sciences, University of Teramo, Italy
2   IRCCS C. Mondino, Mondino-Tor Vergata Center for Experimental Neurobiology, Rome, Italy
,
Anna Fiori
3   Departments of Biochemical Sciences “A. Rossi Fanelli”, University of Rome La Sapienza, Italy
,
Monica Bari
1   Department of Biomedical Sciences, University of Teramo, Italy
,
Filippo Granata
4   Departments of Cellular and Developmental Biology, University of Rome La Sapienza, Italy
,
Valeria Gasperi
5   Department of Experimental Medicine and Biochemical Sciences, University of Rome Tor Vergata, Italy
,
M. Egle De Stefano
4   Departments of Cellular and Developmental Biology, University of Rome La Sapienza, Italy
,
Alessandro Finazzi-Agrò
5   Department of Experimental Medicine and Biochemical Sciences, University of Rome Tor Vergata, Italy
,
Roberto Strom
6   Departments of Cellular Biotechnology and Hematology, University of Rome La Sapienza, Italy
› InstitutsangabenFinancial support: This investigation was supported by the Ministero dell’Istruzione, dell’Università e della Ricerca (Cofin 2003 to M.M. and Cofin 2004 to R.S.), by the University of Rome “La Sapienza” (“Progetto di Ateneo” and “Progetto di Facoltà” to R.S.), by the Istituto Superiore di Sanità (AIDS project 2004 to A.F.-A.), and by Fondazione della Cassa di Risparmio di Teramo (TERCAS 2004 and 2005 to M.M.).
Weitere Informationen

Publikationsverlauf

Received 13. Juni 2005

Accepted after resubmission 04. November 2005

Publikationsdatum:
28. November 2017 (online)

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Summary

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 immunoelectronmicroscopy 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.

Keywords

Brain - directional uptake - endocannabinoids - endothelial cells - nitric oxide - receptors - transporters
 

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