Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Gokasho Uji, Kyoto, Japan.
FEBS Lett. 2010 Feb 5;584(3):599-604. doi: 10.1016/j.febslet.2009.12.008. Epub 2009 Dec 23.
We found that Tyr-Leu (YL) dose-dependently exhibits potent anxiolytic-like activity (0.1-1mg/kg, i.p.) comparable to diazepam in the elevated plus-maze test in mice. YL was orally active (0.3-3mg/kg). A retro-sequence peptide or a mixture of Tyr and Leu was inactive. The anxiolytic-like activity of YL was inhibited by antagonists for serotonin 5-HT(1A), dopamine D(1) and GABA(A) receptors; however, YL had no affinity for them. We also determined the order of their activation is 5-HT(1A), D(1) and GABA(A) receptors using selective agonists and antagonists. Taken together, YL may exhibit anxiolytic-like activity via activation of 5-HT(1A), D(1) and GABA(A) receptors.
我们发现 Tyr-Leu（YL）在小鼠高架十字迷宫试验中具有剂量依赖性的抗焦虑样活性（0.1-1mg/kg，腹腔注射），与安定相当。YL 具有口服活性（0.3-3mg/kg）。反向序列肽或 Tyr 和 Leu 的混合物没有活性。YL 的抗焦虑样活性被 5-HT1A、多巴胺 D1 和 GABA A 受体拮抗剂抑制；然而，YL 对它们没有亲和力。我们还使用选择性激动剂和拮抗剂确定了它们的激活顺序为 5-HT1A、D1 和 GABA A 受体。综上所述，YL 可能通过激活 5-HT1A、D1 和 GABA A 受体来发挥抗焦虑样作用。
