Cannabinoid Receptor Signaling 69ipate in signal transduction via scaffolding mechanisms, including regulation of
MAPK signaling to the nucleus via transcription factors. These receptors promote
intercellular signaling via NO, a diffusible ligand that can impact properties of
neighboring cells. Chronic administration of cannabinoid receptor agonists can
orchestrate pleiotropic changes in cellular signal transduction that contribute to
synaptic plasticity in the processes of learning and memory, cognition, nocicep-
tion, and other responses to CB 1 receptor stimulation.
Future studies should elucidate additional signal transduction pathways in
which the cannabinoid receptors can participate. G proteins other than Gi, Go,
Gs, and Gq may be important in initiating signal transduction pathways that have
not yet been considered for these receptors. Transactivation of alternative signal
transduction pathways, with or without the participation of G proteins, may be
discovered to be important for cannabinoid receptor-mediated responses. Non-
G protein-mediated signal transduction mechanisms may represent alternative
cellular signaling pathways. As we continue to learn more about other cellular pro-
teins with which the cannabinoid receptors can potentially interact, we will have a
better appreciation of both physiological and pathological processes mediated by
endocannabinoid compounds.
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