RT Journal Article SR Electronic T1 Anti-Inflammatory Properties of CB1-Receptor Antagonist Involves β2 Adrenoceptors JF Journal of Pharmacology and Experimental Therapeutics JO J Pharmacol Exp Ther FD American Society for Pharmacology and Experimental Therapeutics SP 445 OP 453 DO 10.1124/jpet.109.163998 VO 333 IS 2 A1 Stephen J. Mnich A1 Ronald R. Hiebsch A1 Rita M. Huff A1 Shanmugam Muthian YR 2010 UL http://jpet.aspetjournals.org/content/333/2/445.abstract AB Antagonists of the cannabinoid receptor 1 (CB1) impart anti-inflammatory activity even though, paradoxically, CB2 receptors are more predominant on cells of the immune system. We attempted to understand the mechanism of this activity by using an acute model of lipopolysaccharide-induced inflammation/stress in both rat and mouse, with selective antagonists to CB1 receptors. We demonstrate that the ability of a CB1 antagonist to inhibit release of proinflammatory cytokines is not dependent on either adrenal-derived catecholamines or corticosteroids or input from the pituitary or thymus glands but does involve the spleen. Furthermore, we show that the anti-inflammatory activity is retained without communication from the central nervous system following ganglionic blockade, suggesting a peripheral site of action. Finally, we show that the anti-inflammatory activity can be inhibited with the use of a selective β2-adrenoceptor antagonist. Copyright © 2010 by The American Society for Pharmacology and Experimental Therapeutics