Cannabinoid and cannabinoid-like receptors in microglia, astrocytes, and astrocytomas

Abstract

CB1 and CB2 receptors are activated by a plethora of cannabinoid compounds, be they endogenously-produced, plant-derived or synthetic. These receptors are expressed by microglia, astrocytes and astrocytomas, and their activation regulates these cells' differentiation, functions and viability. Recent studies show that glial cells also express cannabinoid-like receptors, and that their activation regulates different cell functions, but also control cell viability. This review summarizes this evidence, and discusses how selective compounds targeting cannabinoid-like receptors constitute promising therapeutics to manage neuroinflammation and eradicate malignant astrocytomas. Importantly, the selective targeting of cannabinoid-like receptors should provide therapeutic relieve without inducing the typical psychotropic effects and possible addictive properties associated with the use of Delta9-tetrahydrocannabinol, the main psychotropic ingredient produced by the plant Cannabis sativa.

Figure 1

Chemical structure of prototypical cannabinoids

Figure 2

Molecularly identified receptors activated by cannabinoids

Figure 3

Cannabinoid-like receptors expressed by microglia. PEA activates a G_i/o-protein coupled receptor that inhibits adenylyl cyclase activity, Abn-CBD and 2-AG activate, while O-1918 antagonizes, a G_i/o-protein coupled receptor that activates Erk. Both reduction in cAMP and activation of Erk stimulate microglial cell migration.

Figure 4

Cannabinoid-like receptors expressed by astrocytes. Anandamide (AEA) activates a G_i/o-protein coupled receptor that inhibits adenylyl cyclase activity, WIN regulates nitric oxide (NO) production through an unknown receptor, and anandamide closes gap junction through an unknown receptor.

Figure 5

Cannabinoid-like receptors expressed by astrocytomas. Hu-311 induces apoptosis through an unknown receptor, and CBD both induces apoptosis and inhibits cell migration.