58
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.)
