Pfizer Global Research and Development, Chesterfield, Missouri 63017, USA.
J Pharmacol Exp Ther. 2010 May;333(2):445-53. doi: 10.1124/jpet.109.163998. Epub 2010 Feb 17.
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.
大麻素受体 1 (CB1) 的拮抗剂具有抗炎活性，尽管矛盾的是，CB2 受体在免疫系统细胞中更为主要。我们试图通过使用脂多糖诱导的炎症/应激的急性模型在大鼠和小鼠中，用 CB1 受体的选择性拮抗剂来理解这种活性的机制。我们证明，CB1 拮抗剂抑制促炎细胞因子释放的能力不依赖于肾上腺源性儿茶酚胺或皮质激素，也不依赖于垂体或胸腺的输入，但确实涉及脾脏。此外，我们表明，抗炎活性在神经节阻断后没有中枢神经系统的通讯仍能保留，提示作用部位在外周。最后，我们表明，抗炎活性可以用选择性β2-肾上腺素能受体拮抗剂来抑制。
