| Autor: |
Mnich SJ; Pfizer Global Research and Development, Chesterfield, Missouri 63017, USA. stephen.j.mnich@pfizer.com, Hiebsch RR, Huff RM, Muthian S |
| Jazyk: |
angličtina |
| Zdroj: |
The Journal of pharmacology and experimental therapeutics [J Pharmacol Exp Ther] 2010 May; Vol. 333 (2), pp. 445-53. Date of Electronic Publication: 2010 Feb 17. |
| DOI: |
10.1124/jpet.109.163998 |
| Abstrakt: |
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 beta2-adrenoceptor antagonist. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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