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Thromb Haemost 2006; 95(01): 117-127
DOI: 10.1160/TH05-06-0413
DOI: 10.1160/TH05-06-0413
Endothelium and Vascular Development
Regulation by cannabinoid receptors of anandamide transport across the blood-brain barrier and through other endothelial cells
Financial 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.).
Further Information
Publication History
Received
13 June 2005
Accepted after resubmission
04 November 2005
Publication Date:
28 November 2017 (online)
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.
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