Anandamide Metabolism and Transport
Anandamide and 2-AG are endogenous compound that binds to the cannabinoid receptor as does THC, the active component of marijuana. Anandamide and 2-AG are very important neurotransmitter since they affects mood, memory, pain, appetite, response to stress, and many other physiological processes. My laboratory described the enzyme in the brain that hydrolyzes anandamide in 1993. It is now called FAAH, an abbreviation for the fatty acid amide hydrolase. Over the years we have undertaken basic research to understand how FAAH works to regulate anandamide levels. With the long-term goal of developing drugs to regulate the endocannabinoids, we are now turning our attention to studying the mechanism by which anandamide is transported by the fatty acid binding proteins (FABPs) from the membrane to FAAH inside the cell. We are also interested in the synthesis of anandamide and are now characterizing a conditional NAPE-PLD KO animal.
Figure: Scheme demonstrating anandamide inactivation and FABP drug target.
Anandamide crosses the membrane by diffusion but requires FABPs for transport through the cytoplasm to the endoplasmic reticulum for breakdown by FAAH. FABP inhibitors prevent AEA from being delivered to FAAH for breakdown resulting in increased AEA levels at the receptor.
Berger WT, Ralph BP, Kaczocha M, Sun J, Balius TE, et al. (2012) Targeting Fatty Acid Binding Protein (FABP) Anandamide Transporters – A Novel Strategy for Development of Anti-Inflammatory and Anti-Nociceptive Drugs. PLoS ONE 7(12): e50968. doi:10.1371/journal.pone.0050968. [link]