Leptin inhibits norepinephrine efflux from the hypothalamus in vitro: role of gamma aminobutyric acid
Leptin inhibits norepinephrine efflux from the hypothalamus in vitro: role of gamma aminobutyric acid
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DOI：
10.1016/j.brainres.2004.07.010
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发表时间：
2004-09-24
期刊：
影响因子：
2.9
通讯作者：
MohanKumar, PS
中科院分区：
文献类型：
--
作者：
Francis, J;MohanKumar, SMJ;MohanKumar, PS
瘦素是一种由脂肪细胞分泌的激素，会产生许多中枢和神经内分泌效应，其背后的机制尚不完全清楚。下丘脑去甲肾上腺素 (NE) 参与许多与瘦素相关的神经内分泌作用。因此，我们推测瘦素可能通过影响下丘脑NE活性而发挥中枢和神经内分泌作用。由于已知γ氨基丁酸 (GABA) 会影响 NE 的释放，因此我们还测试了瘦素诱导的 NE 变化可能通过 GABA 介导的可能性。将成年雄性大鼠的中基底下丘脑在体外培养系统中在 95% O-2 和 5% CO2 的气氛中在 Krebs Ringers Henseleit (KRH) 溶液中于 37°C 下培养四个连续培养期，每次 60 分钟。确定基础释放后，在第二个潜伏期用 0、0.1、1 或 10 nm 瘦素、荷包牡丹碱（GABA-A 受体拮抗剂；10 μM）和荷包牡丹碱（10 μM）+10 nM 瘦素攻击下丘脑。在第三次孵育中测量瘦素的残留效应，其中组织单独与KRH一起孵育，并且在第四次孵育中当组织暴露于高K+KRH时测定组织的活力。使用具有电化学检测功能的高效液相色谱法 (HPLC-EC) 测量培养介质中的 NE 水平。瘦素以剂量依赖性方式抑制下丘脑的 NE 流出。此外，用 10 nM 瘦素和荷包牡丹碱孵育下丘脑，完全阻断了瘦素诱导的 NE 外流减少。这些结果首次证明瘦素可以直接作用于下丘脑，通过 GABA 抑制 NE 外流。结论是瘦素可能通过调节下丘脑的NE和GABA水平产生中枢和神经内分泌作用。 (C) 2004 年由 Elsevier B.V. 出版
Leptin, a hormone secreted by adipocytes, produces a number of central and neuroendocrine effects, the mechanisms behind which are not completely understood. Hypothalamic norepinephrine (NE) is involved in many of the neuroendocrine effects that are associated with leptin. Therefore, we hypothesized that leptin could affect hypothalamic NE activity to bring about its central and neuroendocrine effects. Because gamma aminobutyric acid (GABA) is known to affect the release of NE, we also tested the possibility that leptin-induced changes in NE could be mediated through GABA. The mediobasal hypothalami from adult male rats were incubated in an in vitro incubation system for four consecutive incubation periods of 60 min each at 37 C in Krebs Ringers Henseleit (KRH) solution in an atmosphere of 95% O-2 and 5% CO2. After determining the basal release, the hypothalami were challenged with 0, 0.1, 1 or 10 nm of leptin, bicuculline (a GABA-A receptor antagonist; 10 muM) and bicuculline (10 muM) +10 nM of leptin during the second incubation period. Residual effects of leptin were measured in the third incubation where tissues were incubated with KRH alone, and the viability of tissues was determined in the fourth incubation when tissues were exposed to high K+ KRH. NE levels in the incubation medium were measured using high-performance liquid chromatography with electrochemical detection (HPLC-EC). Leptin inhibited NE efflux from the hypothalamus in a dose-dependent manner. Moreover, incubation of hypothalami with 10 nM of leptin and bicuculline, completely blocked the leptin-induced decrease in NE efflux. These results demonstrate for the first time that leptin could act directly on the hypothalamus to inhibit NE efflux through GABA. It was concluded that leptin could probably produce its central and neuroendocrine effects by modulating NE and GABA levels in the hypothalamus. (C) 2004 Published by Elsevier B.V.