Nitric oxide inhibits the release of norepinephrine and dopamine from the medial basal hypothalamus of the rat.
Nitric oxide inhibits the release of norepinephrine and dopamine from the medial basal hypothalamus of the rat.
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DOI：
10.1073/pnas.92.24.11299
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发表时间：
1995-11
影响因子：
11.1
通讯作者：
A. Seilicovich;M. Lasaga;M. Befumo;B. Duvilanski;M. del Carmen Díaz;V. Rettori;S. Mccann
中科院分区：
文献类型：
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作者：
A. Seilicovich;M. Lasaga;M. Befumo;B. Duvilanski;M. del Carmen Díaz;V. Rettori;S. Mccann
先前的研究表明，去甲肾上腺素和多巴胺刺激黄体生成素（LH）释放激素（LHRH）的释放，然后通过垂体门脉血管到达腺垂体释放 LH。去甲肾上腺素通过 α1-肾上腺素能受体发挥作用，该受体刺激内侧基底下丘脑 (MBH) 的一氧化氮能 (NOergic) 神经元释放一氧化氮 (NO)。 NO 激活鸟苷酸环化酶和环氧合酶，从而诱导 LHRH 释放到垂体门静脉血管中。我们测试了这两种儿茶酚胺通过局部反馈调节 NO 释放的假设。 MBH 外植体在硝普钠 (NP)（一种 NO 释放剂）存在下进行培养，并测定对儿茶酚胺释放的影响。 NP抑制去甲肾上腺素的释放。通过将组织与NO清除剂血红蛋白（20微克/毫升）一起孵育，可以增加基础释放。血红蛋白也阻断了NP的抑制作用。在存在使细胞膜去极化的高钾 (40 mM) 介质的情况下，去甲肾上腺素的释放增加了 3 倍，并且这被 NP 显着抑制。血红蛋白再次导致去甲肾上腺素释放进一步增加，并阻断 NP 的作用。当组成型NO合酶被竞争性抑制剂NG-单甲基-L-精氨酸（NMMA）以300μM抑制时，去甲肾上腺素的基础释放增加，钾诱发的释放也增加，并且在后一种情况下，这与组织浓度的降低有关，可能是因为在NMMA存在的情况下，合成无法跟上释放的增加。结果与多巴胺非常相似，只是 NP 对钾诱发的多巴胺释放的减少并不显着。然而，与血红蛋白一起孵育后的增加是显着的，并且当与单独的NP一起孵育时，血红蛋白导致多巴胺释放显着升高。在这种情况下，NP 增加了多巴胺的组织浓度，同时抑制了释放，表明合成仍在继续，从而在释放减少的情况下提高了组织浓度。当组织与 NP 加血红蛋白一起孵育时，导致释放增加高于单独使用 NP 所获得的释放量，与不存在血红蛋白的情况相比，组织浓度显着下降，表明随着释放的增加，释放超过合成，导致组织浓度下降。当 NMMA 阻断 NO 合酶时，在基础条件或钾诱发条件下，多巴胺的释放都会增加。同样，在后一种情况下，组织浓度显着下降，可能是因为合成与释放不匹配。因此，两种儿茶酚胺的结果非常相似，表明 NO 可以抑制两种胺的释放。由于两种儿茶酚胺都会激活LHRH的释放，NO对其释放的抑制形成超短环负反馈，NO抑制儿茶酚胺的释放，从而减少NO能神经元的激活并减少LHRH的释放。这可能是终止 LHRH 释放脉冲的重要手段，LHRH 产生脉冲式释放 LH，刺激雄性和雌性哺乳动物的性腺功能。
Previous research indicates that norepinephrine and dopamine stimulate release of luteinizing hormone (LH)-releasing hormone (LHRH), which then reaches the adenohypophysis via the hypophyseal portal vessels to release LH. Norepinephrine exerts its effect via alpha 1-adrenergic receptors, which stimulate the release of nitric oxide (NO) from nitricoxidergic (NOergic) neurons in the medial basal hypothalamus (MBH). The NO activates guanylate cyclase and cyclooxygenase, thereby inducing release of LHRH into the hypophyseal portal vessels. We tested the hypothesis that these two catecholamines modulate NO release by local feedback. MBH explants were incubated in the presence of sodium nitroprusside (NP), a releaser of NO, and the effect on release of catecholamines was determined. NP inhibited release of norepinephrine. Basal release was increased by incubation of the tissue with the NO scavenger hemoglobin (20 micrograms/ml). Hemoglobin also blocked the inhibitory effect of NP. In the presence of high-potassium (40 mM) medium to depolarize cell membranes, norepinephrine release was increased by a factor of 3, and this was significantly inhibited by NP. Hemoglobin again produced a further increase in norepinephrine release and also blocked the action of NP. When constitutive NO synthase was inhibited by the competitive inhibitor NG-monomethyl-L-arginine (NMMA) at 300 microM, basal release of norepinephrine was increased, as was potassium-evoked release, and this was associated in the latter instance with a decrease in tissue concentration, presumably because synthesis did not keep up with the increased release in the presence of NMMA. The results were very similar with dopamine, except that reduction of potassium-evoked dopamine release by NP was not significant. However, the increase following incubation with hemoglobin was significant, and hemoglobin, when incubated with NP, caused a significant elevation in dopamine release above that with NP alone. In this case, NP increased tissue concentration of dopamine along with inhibiting release, suggesting that synthesis continued, thereby raising the tissue concentration in the face of diminished release. When the tissue was incubated with NP plus hemoglobin, which caused an increase in release above that obtained with NP alone, the tissue concentration decreased significantly compared with that in the absence of hemoglobin, indicating that, with increased release, release exceeded synthesis, causing a fall in tissue concentration. When NO synthase was blocked by NMMA, the release of dopamine, under either basal or potassium-evoked conditions, was increased. Again, in the latter instance the tissue concentration declined significantly, presumably because synthesis did not match release. Therefore, the results were very similar with both catecholamines and indicate that NO acts to suppress release of both amines. Since both catecholamines activate the release of LHRH, the inhibition of their release by NO serves as an ultra-short-loop negative feedback by which NO inhibits the release of the catecholamines, thereby reducing the activation of the NOergic neurons and decreasing the release of LHRH. This may be an important means for terminating the pulses of release of LHRH, which generate the pulsatile release of LH that stimulates gonadal function in both male and female mammals.