Intracellular trafficking of anandamide: new concepts for signaling

Endocannabinoids are key mediators of many aspects of human health and disease. The biological activity of anandamide, a prominent member of this group, depends on the metabolic control exerted by biosynthetic, catabolic and oxidative pathways working together. Cellular uptake and intracellular trafficking of anandamide are crucial steps in the process. Whereas the identity of anandamide transmembrane carriers remains undetermined, recent insights have been gained related to its intracellular stores (adiposomes) and intracellular binding proteins, particularly fatty acid binding proteins, albumin and heat shock protein 70. On this basis, we propose a reconsideration of the dogma that endocannabinoids are exclusively synthesized and released 'on demand', and suggest that their metabolic control is complemented by intracellular trafficking and storage in specific reservoirs.