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Chapter 1: Neural Sciences

Figure 1.4-15 Retrograde neurotransmission of the endocannabinoids, anandamide, and 2-arachidonylglycerol (2-AG). Anandamide is synthesized on demand for neurotransmission via a two-step process. The enzyme NAT transfers the arachidonic acid chain from a phospholipid (APL) to phosphatidylethanolamine (PE), thereby producing NAPE. A second enzyme, NAPE-PLD, generates anandamide. 2-AG is similarly synthesized in two steps by the enzymes PLC and DAGL. The endocannabinoids made in a postsynaptic neuron cross the synapse and activate presynaptic CB1 receptors, and suppress neurotransmission of the presynaptic neuron (although activation of the presynaptic neu- ron occurs in some cases). Enzymes involved in endocannabinoid synthesis are yellow, those that break them down in red. 2-AG is pre- dominantly inactivated in the presynaptic neuron by MAGL, whereas anandamide is destroyed in the postsynaptic neuron by FAAH. PE, phosphatidylethanolamine; APL, arachidonyl phospholipids; NAT, N -acyltransferase; NAPE, N -arachidonyl-phosphatidylethanolamine; NAPE-PLD, N -arachidonyl-phosphatidylethanolamine phospholipase D; FAAH, fatty acid amide hydrolase; MAGL, monoacylglycerol lipase; PLC, phospholipase C; DAG, diacylglycerol; DAGL, diacylglycerol lipase; R 1 -R 3 , various acyl or akyl side chains of phospholipids; R’, side chain of phospholipid head group. (From Sadock BJ, SadockVA, Ruiz P. Kaplan & Sadock’s Comprehensive Textbook of Psychiatry . 9 th ed. Philadelphia: Lippincott Williams & Wilkins; 2009:112.)