Ataturk University, Faculty of Medicine, Department of Pharmacology, Erzurum, Turkey.
Eur J Pharmacol. 2013 Sep 5;715(1-3):270-9. doi: 10.1016/j.ejphar.2013.05.010. Epub 2013 Jun 3.
The aim of this study was: (1) to investigate possible role for 5-HT7 receptors in carrageenan induced inflammatory paw oedema in rats; (2) to determine the presence of 5-HT7 receptors in rat paw tissue; (3) to observe the effects of 5-HT7 receptor agonist and antagonist administration on inflammation; and (4) to determine a unique mechanism for inflammatory processes via 5-HT7 receptors. Effects of 5-HT7 receptor agonist, antagonist and indomethacin were investigated in carrageenan induced paw oedema in rats. Blood and tissue samples were collected and evaluated biochemically for serum cytokine levels, tissue oxidant-antioxidant balance and histopathologically for inflammatory cell accumulation. We performed Real Time PCR analyses for tissue 5-HT7 receptor and COX mRNA expressions. The 5-HT7 receptor agonist AS-19 exerted significant anti-inflammatory effect both alone and in combination with indomethacin. Antagonist, SB269970, did not affect inflammation alone but decreased the effects of agonist when co-administered. 5-HT7 mRNA levels were higher in the carrageenan group than healthy control. Carrageenan+indometacin group decreased the mRNA expression of 5-HT7 when compared to carrageenan group. While agonist administration decreased 5-HT7 mRNA expression when compared to carrageenan group. Agonist decreased paw COX expression. Agonist also decreased serum cytokine levels and tissue oxidative stress. In conclusion, this study demonstrated for the first time that 5-HT7 receptors are expressed in rat paw tissue and that this expression responds to inflammatory stimuli. The 5-HT7 receptor may be a promising new therapeutic target for prevention of inflammation and inflammatory disorders and may also provide a new glimpse into inflammation pathophysiology.
(1) 探讨 5-HT7 受体在角叉菜胶诱导的大鼠炎性足肿胀中的可能作用；(2) 确定 5-HT7 受体在大鼠足组织中的存在；(3) 观察 5-HT7 受体激动剂和拮抗剂给药对炎症的影响；(4) 通过 5-HT7 受体确定炎症过程的独特机制。研究了 5-HT7 受体激动剂、拮抗剂和吲哚美辛对角叉菜胶诱导的大鼠足肿胀的影响。采集血液和组织样本，进行生化评估血清细胞因子水平、组织氧化应激-抗氧化平衡，以及组织病理学评估炎症细胞聚集。我们进行了组织 5-HT7 受体和 COX mRNA 表达的实时 PCR 分析。5-HT7 受体激动剂 AS-19 单独使用和与吲哚美辛联合使用均具有显著的抗炎作用。拮抗剂 SB269970 单独使用时不影响炎症，但与激动剂联合使用时会降低其作用。与健康对照组相比，角叉菜胶组大鼠组织中 5-HT7 受体 mRNA 水平较高。与角叉菜胶组相比，角叉菜胶+吲哚美辛组降低了 5-HT7 的 mRNA 表达。而激动剂与角叉菜胶组相比，降低了 5-HT7 mRNA 表达。激动剂降低了足 COX 的表达。激动剂还降低了血清细胞因子水平和组织氧化应激。总之，本研究首次证明 5-HT7 受体在大鼠足组织中表达，并且这种表达对炎症刺激有反应。5-HT7 受体可能是预防炎症和炎症性疾病的有前途的新治疗靶点，也可能为炎症病理生理学提供新的见解。
