Zhao Hui, Ohinata Kousaku, Yoshikawa Masaaki
Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Kyoto 611-0011, Japan.
Prostaglandins Other Lipid Mediat. 2009 Apr;88(3-4):68-72. doi: 10.1016/j.prostaglandins.2008.10.001. Epub 2008 Oct 21.
We found that prostaglandin (PG) D(2), the most abundant PG produced in the central nervous system (CNS), exhibited anxiolytic-like activity at a dose of 10-100pmol/mouse after intracerebroventricular (i.c.v.) administration in the elevated plus-maze test in mice. A DP(1) receptor-selective agonist, BW245C, mimicked the anxiolytic-like activity of PGD(2), while a DP(2) receptor agonist 13,14-dihydro-15-keto-PGD(2) was inactive. The anxiolytic-like activity of PGD(2) was blocked by a DP(1) antagonist, BWA868C, suggesting that PGD(2)-induced anxiolytic-like activity was mediated by the DP(1) receptor. Adenosine A(2A) or GABA(A) receptor antagonists, SCH58261 or bicuculline, respectively, also blocked its anxiolytic-like activity. Taken together, centrally administered PGD(2) may induce anxiolytic-like activity via the A(2A) and GABA(A) receptors, downstream of the DP(1) receptor.
我们发现，前列腺素（PG）D2是中枢神经系统（CNS）中产生的最丰富的PG，在小鼠高架十字迷宫试验中，经脑室内（i.c.v.）给药后，剂量为10 - 100 pmol/小鼠时表现出抗焦虑样活性。DP（1）受体选择性激动剂BW245C模拟了PGD2的抗焦虑样活性，而DP（2）受体激动剂13,14 - 二氢 - 15 - 酮 - PGD2无活性。PGD2的抗焦虑样活性被DP（1）拮抗剂BWA868C阻断，表明PGD2诱导的抗焦虑样活性是由DP（1）受体介导的。腺苷A（2A）或GABA（A）受体拮抗剂SCH58261或荷包牡丹碱也分别阻断了其抗焦虑样活性。综上所述，中枢给予的PGD2可能通过DP（1）受体下游的A（2A）和GABA（A）受体诱导抗焦虑样活性。
