Complement C5a exhibits anxiolytic-like activity via the prostaglandin D₂鈭扗P₁ receptor system coupled to adenosine A_2A and GABA_A receptors

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• 作者：Chihiro Miyamoto^a ; ^b ; Mariko Yoshida^a ; ^b ; Masaaki Yoshikawa^a ; ^b ; Takafumi Mizushige^a ; ^c ; Kousaku Ohinata^a ; ^b ; ^{ohinata@kais.kyoto-u.ac.jp}
• 关键词：Anxiolytic activity ; Complement C5a ; Prostaglandin D2 ; DP1 receptor ; Adenosine A2A receptor ; GABAA receptor
• 刊名：Prostaglandins and Other Lipid Mediators
• 出版年：2012
• 期刊代码：31_10988823
• 类别：bio
• 出版时间：May, 2012
• 卷：98
• 期：1-2
• 页码：17-22
• 文件大小：882 K

摘要

We have recently found that central PGD₂ exhibits anxiolytic-like activity. Here we show that complement C5a exhibits anxiolytic-like activity via the PGD₂ system. Centrally administered C5a had anxiolytic-like activity at a dose of 0.3 pmol/mouse in the elevated plus-maze test in mice. C5a-induced anxiolytic-like activity was inhibited by indomethacin, a cyclooxygenase inhibitor, or BWA868C, an antagonist of DP₁ receptor for PGD₂, respectively. The anxiolytic effect of C5a was also blocked by SCH58261 or bicuculline, antagonists of adenosine A_2A and GABA_A receptors, respectively, which were activated downstream of PGD₂-DP₁ receptor. These results suggest that C5a exhibits anxiolytic-like activity via the PGD₂-DP₁ receptor system coupled to the activation of adenosine A_2A and GABA_A receptors.