Figure 1.

The endocannabinoids (eCBs) AEA and 2-AG are produced on demand from lipid precursors and released to the extracellular space. Endogenous and exogenous cannabinoids act through the same signaling systems: Binding to Gi-coupled receptors CB1 or CB2 modulates intracellular cascades and leads for example to the inhibition of adenylyl cyclase (AC) or the regulation of transcription through extracellular signal-regulated kinases (ERKs). Alternative receptors are non-CB1/2 GPCRs, non-GPCRs like TRPV1 and, intracellularly, mitochondrial CB1 (mtCB1) and peroxisome proliferator-activated receptors (PPARs). Signaling is terminated through hydrolysis, but eCBs might also serve as substrates for cyclooxygenases (COXs), lipoxygenases (LOXs) or cytochromes P450 (P450), yielding additional bioactive compounds. Note that all illustrated processes do not have to take place in distinct cells as autocrine eCB signaling has been shown as well. Abbreviations: PIP2 phosphatidylinositol 4,5-bisphosphate, IP3 inositol-1,4,5-trisphosphat, DAG Diacylglycerol, PLC phospholipase C, DAGL diacylglycerol lipase, 2-AG 2-arachidonylglycerol, PC phosphatidylcholine, PE phosphatidylethanolamine, AA arachidonic acid, NAPE N-arachidonoyl phosphatidylethanolamine, NAPE-PLD NAPE-specific phospholipase D, MAGL monoacylglycerol lipase, FAAH fatty acid amide hydrolase.