Inflammation and peripheral 5-HT₇ receptors: The role of 5-HT₇ receptors in carrageenan induced inflammation in rats
2013
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.
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