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(1) receptors, which are known to modulate cell migration. To determine if cannabinoid CB(1) receptors expressed by microglial cells modulate their migration, we assessed whether arachidonylcyclopropylamide (ACPA, an agonist shown to selectively activate CB(1) 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 (EC(50)=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 CB(1) receptor antagonist N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamidehydrochloride (SR141716A) did not prevent ACPA-induced BV-2 cell migration. Two antagonists of cannabinoid CB(2) 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 CB(2) receptors and abn-CBD receptors, rather than cannabinoid CB(1) receptors, regulate microglial cell migration, and that ACPA is a broad cannabinoid receptor agonist.
Franklin
Allyn
A
Department of Pharmacology, University of Washington, Seattle, WA 98195-7280, USA.
Stella
Nephi
N
D000818:Animals; D001095:Arachidonic Acids / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects* / Q000502:physiology; D051379:Mice; D017628:Microglia / Q000187:drug effects* / Q000502:physiology; D043885:Receptor, Cannabinoid, CB2 / Q000819:agonists / Q000502:physiology*; D012118:Resorcinols / Q000494:pharmacology*
C479832:4-(3-3,4-p-menthadien-(1,8)-yl)olivetol; D001095:Arachidonic Acids; D043885:Receptor, Cannabinoid, CB2; D012118:Resorcinols; C119324:arachidonylcyclopropylamide