Lipopolysaccharide and cyclic AMP regulation of CB2 cannabinoid receptor levels in rat brain and mouse RAW 264.7 macrophages

CB2 cannabinoid receptors exist in immune cells including macrophages. Affinity-purified antibodies against the CB2 receptor identified a 45 kDa protein in rat brain, human tonsil and rat and mouse microglia, but not mouse N18TG2 neuroblastoma cells. Intracerebroventricular lipopolysaccharide (LPS) increased immunoreactive CB2 receptors in brain membranes detected by Western blot. LPS increased immunodetectable CB2 receptors in cultured RAW 264.7 macrophages, and this was partially attenuated by cyclohexamide or the protein kinase A and C inhibitors H8 and bis-indolylmaleimide. Forskolin or dibutyryl cyclic AMP increased CB2 receptor immunoreactivity, suggesting the involvement of the cyclic AMP–protein kinase A–Cyclic AMP response element pathway in the regulation of CB2 receptor levels.