Mechanism
Like the CB1 receptors, CB2 receptors inhibit the activity of adenylyl cyclase through their Gi/Goα subunits. Through their Gβγ subunits, CB2 receptors are also known to be coupled to the MAPK-ERK pathway, a complex and highly conserved signal transduction pathway, which critically regulates a number of important cellular processes in both mature and developing tissues. Activation of the MAPK-ERK pathway by CB2 receptor agonists acting through the Gβγ subunit ultimately results in changes in cell migration as well as in an induction of the growth-related gene Zif268 (also known as Krox-24, NGFI-A, and egr-1). The Zifi268 gene encodes a transcriptional regulator implicated in neuroplasticity and long term memory formation.
At present, there are five recognized cannabinoids produced endogenously throughout the body: Arachidonoylethanolamine (anandamide), 2-arachidonoyl glycerol (2-AG), 2-arachidonyl glyceryl ether (noladin ether), virodhamine, as well as the recently-discovered N-arachidonoyl-dopamine (NADA). Many of these ligands appear to exhibit properties of functional selectivity at the CB2 receptor: 2-AG preferentially activates the MAPK-ERK pathway, while noladin preferentially inhibits adenylyl cyclase. Like noladin, the synthetic ligand CP-55,940 has also been shown to preferentially inhibit adenylyl cyclase in CB2 receptors. Together, these results support the emerging concept of agonist-directed trafficking at the cannabinoid receptors.
Read more about this topic: Cannabinoid Receptor Type 2
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