Goldfarb J, Walcott J, Blandina P
Department of Pharmacology, Mount Sinai School of Medicine, City University of New York, New York.
J Pharmacol Exp Ther. 1993 Oct;267(1):45-50.
Hypothalamic slices (400 mu) from male Sprague-Dawley rats were perfused with a Mg+(+)-free medium containing nomifensine (10 microM) and tyrosine (50 microM). Spontaneous release of endogenous norepinephrine (NE), measured by high-performance liquid chromatography-electrochemical detection, averaged 102 +/- 13 (N = 76) fmol/mg of protein/3 min. L-Glutamic acid (L-GLU) (1 mM) more than doubled the rate of NE release. Preincubation with serotonin (5-HT) (0.1-10 microM) produced no change in spontaneous NE release but caused a concentration-dependent decrease of L-GLU-induced NE release with a maximal reduction of about 60 to 70%. 2-Methylserotonin, a 5-HT3 receptor agonist (0.07-10 microM), mimicked the 5-HT response. A highly selective 5-HT3 receptor antagonist, (3 alpha-tropanyl)1H-indole-3-carboxylic acid ester, 1 nM, inhibited the effect of both agonists. Neither ritanserin (1 microM) nor methylsergide (1 microM) modified either spontaneous or 1 mM L-GLU-evoked release of NE. However, if added to the superfusion medium simultaneously with 5-HT, they potentiated significantly the inhibition produced by 5-HT. Alpha-methylserotonin (1 microM) if added alone to the perfusion medium had no effect on 1 mM L-GLU-evoked release of NE but reversed the inhibition induced by 1 microM 2-methylserotonin. These observations provide direct evidence of a dual modulation by 5-HT of L-GLU-evoked release of endogenous NE from slices of rat hypothalamus: An inhibition mediated by 5-HT3 receptors and an opposing action mediated by receptors of the 5-HT1C/2 type.
从雄性斯普拉格 - 道利大鼠获取的下丘脑切片（400微米），用含有诺米芬辛（10微摩尔）和酪氨酸（50微摩尔）的无镁离子培养基进行灌注。通过高效液相色谱 - 电化学检测法测定内源性去甲肾上腺素（NE）的自发释放量，平均为102±13（N = 76）飞摩尔/毫克蛋白质/3分钟。L - 谷氨酸（L - GLU）（1毫摩尔）使NE释放速率增加了一倍多。用血清素（5 - HT）（0.1 - 10微摩尔）预孵育，自发NE释放量无变化，但导致L - GLU诱导的NE释放量呈浓度依赖性降低，最大降低约60%至70%。5 - HT3受体激动剂2 - 甲基血清素（0.07 - 10微摩尔）模拟了5 - HT的反应。一种高选择性的5 - HT3受体拮抗剂，（3α - 托烷基）1H - 吲哚 - 3 - 羧酸酯，1纳摩尔，抑制了两种激动剂的作用。利坦色林（1微摩尔）和甲基麦角新碱（1微摩尔）均未改变NE的自发释放或1毫摩尔L - GLU诱发的释放。然而，如果与5 - HT同时添加到灌注培养基中，它们会显著增强5 - HT产生的抑制作用。α - 甲基血清素（1微摩尔）单独添加到灌注培养基中对1毫摩尔L - GLU诱发的NE释放无影响，但可逆转1微摩尔2 - 甲基血清素诱导的抑制作用。这些观察结果提供了直接证据，表明5 - HT对大鼠下丘脑切片中L - GLU诱发的内源性NE释放具有双重调节作用：一种由5 - HT3受体介导的抑制作用和一种由5 - HT1C/2型受体介导的相反作用。
