Department of Pharmacology and Toxicology, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran.
Int Immunopharmacol. 2010 Sep;10(9):1010-6. doi: 10.1016/j.intimp.2010.05.013. Epub 2010 Jun 4.
The antagonists of 5HT(3) receptors have shown impressive efficacy in rheumatoid arthritis, osteoarthritis or fibromyalgia. The mechanistic relationships between 5HT(3) receptors, angiogenesis and sequence of cytokine expression, and leukocyte recruitment during inflammation are not clear. We evaluate the effects of granisetron on inflammatory parameters and angiogenesis in rat air-pouch model.
Male Wistar rats were anesthetized, and then 20 ml and 10 ml of sterile air were injected subcutaneously in the back on day 0 and day 3, respectively. On day 6, inflammation was induced by injection of 1 ml of carrageenan 1% into pouches. After 6 and 72 h, the rats were sacrificed; pouch fluid was collected in order to determine exudate volume, the number of accumulated cells and TNFalpha/PGE(2) concentration. Pouches were dissected out and weighed. Angiogenesis of granulomatous tissue was assayed using a hemoglobin kit.
Leukocyte accumulation was dose-dependently inhibited by granisetron both at 6 and 72 h after induction of inflammation. All doses of granisetron decreased hemoglobin level in the whole granulation tissue in a bell-shaped manner. Vascular network formation was also inhibited by granisetron. Granisetron increased PGE(2) level at a lower dose (50 microg/pouch) but higher doses (100 and 200 microg/pouch) inhibited the release. At the same time, TNFalpha production was decreased by the lower dose and increased by higher doses of granisetron in a reciprocal fashion.
Anti-inflammatory activities of 5HT(3) receptor antagonist, granisetron probably are mediated through modulation of TNFalpha/PGE(2) production and leukocyte infiltration.
5-HT(3) 受体拮抗剂在类风湿关节炎、骨关节炎或纤维肌痛症中显示出显著的疗效。5-HT(3) 受体、血管生成以及细胞因子表达顺序和白细胞募集在炎症过程中的机制关系尚不清楚。我们评估格拉司琼对大鼠气囊模型中炎症参数和血管生成的影响。
雄性 Wistar 大鼠麻醉后，于第 0 天和第 3 天背部皮下注射 20ml 和 10ml 无菌空气。第 6 天，将 1%角叉菜胶 1ml 注入囊中诱导炎症。6h 和 72h 后处死大鼠；收集囊液以测定渗出液体积、聚集细胞数和 TNFalpha/PGE(2)浓度。取出囊并称重。使用血红蛋白试剂盒检测肉芽组织中的血管生成。
白细胞聚集在炎症诱导后 6h 和 72h 均被格拉司琼剂量依赖性抑制。格拉司琼以钟形曲线方式降低整个肉芽组织中的血红蛋白水平。血管网络形成也被格拉司琼抑制。格拉司琼在较低剂量（50μg/囊）时增加 PGE(2)水平，但较高剂量（100 和 200μg/囊）抑制其释放。同时，较低剂量的格拉司琼降低 TNFalpha 产生，而较高剂量的格拉司琼则以相反的方式增加 TNFalpha 产生。
5-HT(3) 受体拮抗剂格拉司琼的抗炎活性可能通过调节 TNFalpha/PGE(2) 产生和白细胞浸润来介导。
