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