Rahman S, McLean J H, Darby-King A, Paterno G, Reynolds J N, Neuman R S
Faculty of Medicine, Memorial University, St. John's, Newfoundland, Canada.
Neuroscience. 1995 Jun;66(4):891-901. doi: 10.1016/0306-4522(95)00002-z.
Using grease gap recordings, age-related changes in serotonin2A receptors were assessed in sensorimotor regions of the cortex by examining serotonin-induced facilitation of the N-methyl-D-aspartate depolarization in cortical wedges prepared from young adult (3-6 months) and senescent (22-34 months) Fisher 344 rats. Serotonin (10-100 microM) facilitated the N-methyl-D-aspartate depolarization in wedges from young adult rats in a concentration-dependent manner, whereas no facilitation was observed in wedges from senescent rats. Similar results were obtained when +/- 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane, a mixed serotonin2A and serotonin2C receptor agonist, was substituted for serotonin. In contrast, agonists at alpha 1A-adrenoceptors, metabotropic glutamate receptors and muscarinic cholinoceptors facilitated the N-methyl-D-aspartate depolarization in wedges from both young adult and senescent rats. Chelerythrine and staurosporine, inhibitors of protein kinase C, but not concanavalin A, myo-inositol or calmodulin antagonists, restored the serotonin facilitation in wedges from senescent animals. In situ hybridization histochemistry revealed that serotonin2A receptor messenger RNA was present in layers II-VI of the cortex, with the highest density of silver grains located in layers III and V of both young adult and senescent rats. Detailed examination of layer V showed that silver grains were significantly higher than background only over pyramidal cells. We conclude that serotonin2A receptors are expressed by pyramidal cells in both young adult and senescent rats and that serotonin acts directly on these receptors to facilitate the N-methyl-D-aspartate depolarization. Moreover, in senescent rats, signal transduction at cortical serotonin2A receptors involved with facilitation of the N-methyl-D-aspartate response is compromised as a result of protein kinase C activation.
通过使用油脂间隙记录法，在从年轻成年（3 - 6个月）和老年（22 - 34个月）的费希尔344大鼠制备的皮质楔形物中，通过检测血清素诱导的N - 甲基 - D - 天冬氨酸去极化的促进作用，评估了皮质感觉运动区域中血清素2A受体的年龄相关变化。血清素（10 - 100微摩尔）以浓度依赖性方式促进年轻成年大鼠楔形物中的N - 甲基 - D - 天冬氨酸去极化，而在老年大鼠的楔形物中未观察到促进作用。当用血清素2A和血清素2C受体混合激动剂±1 - （2,5 - 二甲氧基 - 4 - 碘苯基） - 2 - 氨基丙烷替代血清素时，获得了类似的结果。相反，α1A - 肾上腺素能受体、代谢型谷氨酸受体和毒蕈碱型胆碱能受体的激动剂促进了年轻成年和老年大鼠楔形物中的N - 甲基 - D - 天冬氨酸去极化。蛋白激酶C抑制剂白屈菜红碱和星形孢菌素，但不是伴刀豆球蛋白A、肌醇或钙调蛋白拮抗剂，恢复了老年动物楔形物中的血清素促进作用。原位杂交组织化学显示，血清素2A受体信使核糖核酸存在于皮质的II - VI层，在年轻成年和老年大鼠的III层和V层中银颗粒密度最高。对V层的详细检查表明，仅在锥体细胞上方银颗粒明显高于背景。我们得出结论，血清素2A受体在年轻成年和老年大鼠的锥体细胞中均有表达，并且血清素直接作用于这些受体以促进N - 甲基 - D - 天冬氨酸去极化。此外，在老年大鼠中，由于蛋白激酶C激活，与促进N - 甲基 - D - 天冬氨酸反应相关的皮质血清素2A受体的信号转导受到损害。
