Arachidonylcyclopropylamide increases microglial cell migration through cannabinoid CB2 and abnormal-cannabidiol-sensitive receptors

Microglial cells, the macrophages of the brain, express low, yet detectable levels of cannabinoid CB, receptors, which are known to modulate cell migration. To determine if cannabinoid CB, receptors expressed by microglial cells modulate their migration, we assessed whether arachidonylcyclopropylamide (ACPA, an agonist shown to selectively activate CB, receptors) affects the migration of BV-2 cells, a mouse microglial cell line. We found that ACPA induced a dose-dependent increase in BV-2 cell migration (EC50 = 2.2 nM). This ACPA response was blocked by pertussis toxin pretreatment, suggesting the involvement of G(i/o) protein-coupled receptors. However, the cannabinoid CB1 receptor antagonist N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide-hydrochloride (SR141716A) did not prevent ACPA-induced BV-2 cell migration. Two antagonists of cannabinoid CB2 receptors N-(1,S)-endo-1,3,3-trimethyl bicyclo(2,2,1)heptan-2-yl)-5-(4-chloro-3-methylphenyl)-1-(4-methylbenzyl)-pyrazole-3-carboxamide (SR144528) and cannabinol, as well as two antagonists of the newly identified abnormal-cannabidiol-sensitive (abn-CBD) receptors (O-1918 and cannabidiol) prevented this response. Our results suggest that cannabinoid CB2 receptors and abn-CBD receptors, rather than cannabinoid CB1 receptors, regulate microglial cell migration, and that ACPA is a broad cannabinoid receptor agonist. (C) 2003 Elsevier B.V. All rights reserved.