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5.A
PLC β 4
5.B
PLC β 4
Figure 5. Scheme illustrating the potential mechanisms of receptor-driven endocannabinoid release and
Ca2+-assisted receptor-driven endocannabinoid release. A, In the hippocampus, activation of GluR1/5
or M1/M3 muscarinic receptors stimulates PLCβ1-DAGL cascade and induces the formation of 2-AG.
As a retrograde messenger, 2-AG activates CB1 receptors at presynaptic neuron and suppresses the
GABA release. B, In the cerebellum, activation of mGluR1 receptors in Purkinje cells stimulates LCβ4
by inducing the formation of diacylglycerol (DAG). DAG-lipase (DAGL) converts DAG to 2-AG. 2-
AG activates presynaptic CB1 receptors on parallel fibers and suppresses the glutamate release. These
signaling pathways (A and B) are facilitated by depolarization-induced Ca2+elevation because of the
Ca2+dependency of PLCβ1/4 (Ca2+-assisted receptor-driven endocannabinoid release). PLC,
phospholipase C
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