Fig. (1).

The endocannabinoid system. The drawing represents the distribution in human body of the endocannabinoid components, including the CB₁ and CB₂ cannabinoid receptors, as well as the biosynthesis and degradation enzymatic routes for arachidonoylethanolamine (anandamide, AEA) or 2-arachidonoylglycerol (2-AG) governed by the fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL), respectively. Once synthetized, AEA and 2-AG bind to the cannabinoid receptors via the involvement of membrane transporter (for AEA, anandamide membrane transporter [AMT]). As shown, the presence of the cannabinoid receptors in multiple physiological systems such as brain, lung, gastrointestinal tract, etc. (Panel A) suggest the modulatory role of both receptors in the control of a diversity of complex functions, including memory and learning, brain plasticity, neuronal development, stress and emotions, among many others (Panel B). In addition, the image illustrates that arachidonic acid-containing diacylglycerol (DAG), diacylglycerol lipase (DAGL) synthesizes 2-AG whereas NAPE (N-arachidonoyl phosphatidylethanolamine) and N-acyl phosphatidylethanolamine phospholipase D (NAPE-PLD) participates in the formation of AEA. Once released, both lipids (2-AG and AEA) bind and activate the cannabinoid receptors, which in turn, promotes calcium (Ca²⁺) influx and potassium (K⁺) efflux for modulating neurotransmission (Panel C). (A higher resolution/colour version of this figure is available in the electronic copy of the article).