5-HT_(2C)受体对孵育海马脑片释放分泌型淀粉样前体蛋白的调节

5-HT_(2c) receptor subtype modulate production of secretory β-amyloid protein precursor in incubated rat hippocampal slices

目的 考察5—HT_(2C)受体对孵育海马脑片释放分泌型淀粉样前体蛋白(sAPP)的调节。方法 应用5—HT、特异性5-HT_(2C)受体激动剂M-110及其特异性拮抗L-107孵育海马脑薄片,及Western blot技术和特异性的针对sAPP氨基末端的单克隆抗体22C11检测释放到孵育液中的sAPP。结果 5-HT及特异性5-HT_(2C)受体激动剂M—110在一定的浓度范围内呈浓度依赖性地显著增加sAPP分泌;而特异性5-HT_(2C)受体拮抗剂L-107在一定的浓度范围内则浓度依赖性地显著抑制sAPP分泌。结论 5—HT通过激活5—HT_(2C)受体调节孵育海马脑片分泌型淀粉样前体蛋白的释放。

Aim To determine whether serotonin, a major neurotransmitter in brain, can modulate the production of secretory β-amyloid protein precursor (sAPP) by activation of serotonin 5-HT_(2c) receptor. Methods The hippocampal slices of rats were incubated with various concentrations of serotonin, M-110, or L-107. sAPP released into the incubation medium were assayed by Western blot analysis assay with monoclonal antibody 22C11 for 2 h. Results Various concentrations of serotonin (1.0×10^(-2)-1.0×10~3 μmol·L^(-1)), M-110, a serotonin 5-HT_(2c) agonist (1.5×10^(-6)-1.5×10~3 μmol·L^(-1)), showed positive effect on the production of sAPP while L-107, a serotonin 5-HT_(2c) antagonist (1.0×10^(-9)-1.0×10~3μmol·L^(-1)), showed negative effect on the production of sAPP over controls. Conclusion Serotonin modulates production of secretory amyloid β-protein precursor through serotonin 5-HT_(2c) receptor in incubated rat hippocampal slices.