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. 2012 Mar 14:6:9.
doi: 10.3389/fnbeh.2012.00009. eCollection 2012.

The endocannabinoid system: an overview

Natalia Battista  1 , Monia Di Tommaso, Monica Bari, Mauro Maccarrone
Affiliations

The endocannabinoid system: an overview

Natalia Battista et al. Front Behav Neurosci. .

Abstract

Upon the identification of anandamide (AEA) in the porcine brain, numerous studies contributed to the current state of knowledge regarding all elements that form the "endocannabinoid system (ECS)."How this complex system of receptors, ligands, and enzymes is integrated in helping to regulate fundamental processes at level of central nervous and peripheral systems and how its regulation and dysregulation might counteract disturbances of such functions, is nowadays still under investigation. However, the most recent advances on the physiological distribution and functional role of ECS allowed the progress of various research tools aimed at the therapeutic exploitation of endocannabinoid (eCB) signaling, as well as the development of novel drugs with pharmacological advantages. Here, we shall briefly overview the metabolic and signal transduction pathways of the main eCBs representatives, AEA, and 2-arachidonoylglycerol (2-AG), and we will discuss the therapeutic potential of new ECS-oriented drugs.

Keywords: 2-arachidonoylglycerol; anandamide; endocannabinoids; metabolic pathways; signal transduction.

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Figures

Figure 1
Figure 1
Chemical structures of biologically active eCBs and of the eCB-like compounds.
Figure 2
Figure 2
Schematic representation of the main elements that constitute the endocannabinoid system. The synthesis of N-arachidonoyl-ethanolamine (AEA) is due to the activity of a NAPE-specific phospholipase D (NAPE-PLD), whereas a fatty acid amide hydrolase (FAAH) is responsible for its intracellular degradation to ethanolamine (EtNH2) and arachidonic acid (AA). 2-Arachidonoylglycerol (2-AG) is released from membrane lipids through the activity of diacylglycerol lipase (DAGL), and it is hydrolyzed by a cytosolic monoacylglycerol lipase (MAGL) that releases glycerol and AA. A purported endocannabinoid membrane transporter (EMT) clears AEA and 2-AG from the extracellular space, and takes them up into the cell. Both AEA and 2-AG trigger several signal transduction pathways by acting at their targets, CB1, CB2, GPR55, and nuclear PPARs. AEA, but not 2-AG, binds intracellularly also TRPV1, and thus it is also designated as a true endovanilloid.
Figure 3
Figure 3
The involvement of ECS in some pathophysiological conditions.
See this image and copyright information in PMC

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