Intracellular signaling endocannabinoids

Endocannabinoids are endogenous ligands for the CB1 receptor. The best established are anandamide (N-arachidonoylethanolamine) and 2-AG (2-arachidonoyl-glycerol). Others may also exist. Pathways involved in the formation and inactivation of anandamide and 2-AG are shown in Figure 56-6. Some steps in their formation are Ca2+-dependent. This explains the ability of neuronal depolarization, which increases postsynaptic intracellular Ca2+ levels, to stimulate endocannabinoid formation and release. Some neurotransmitter receptors (e.g. the D2 dopamine receptor) also stimulate endocannabinoid formation, probably by modulating postsynaptic Ca2+ levels or signaling pathways (e.g. PLC) that regulate endocannabinoid formation. 

Endocannabinoids serve as retrograde messengers. They are released by postsynaptic neurons and act on presynaptic CB1 receptors on neighboring nerve terminals. Retrograde signaling by endocannabinoids is essential for many forms of synaptic plasticity that are initiated by postsynaptic depolarization and increased postsynaptic intracellular Ca2+> but expressed as a presynaptic decrease in the probability of transmitter release. Examples include some forms of long-term depression (LTD see Ch. 53) at GABA... 

In summary, the endocannabinoids involved in the types of retrograde endocannabinoid signalling described to date are not fully understood. This will only be resolved by more fully comparing the intracellular cascades involved in the... 

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