N-methyl-D-aspartate (NMDA)-mediated corticotropin-releasing factor (CRF) release in cultured rat amygdala neurons
N-methyl-D-aspartate (NMDA)-mediated corticotropin-releasing factor (CRF) release in cultured rat amygdala neurons
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DOI：
10.1016/s0196-9781(98)00147-8
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发表时间：
1999-01-01
期刊：
影响因子：
3
通讯作者：
Birkle, DL
中科院分区：
文献类型：
--
作者：
Cratty, MS;Birkle, DL
促肾上腺皮质激素释放因子(CRF)在中枢调节应激反应的激活中起重要作用。杏仁核是参与应激反应的边缘结构，有大量的CRF细胞体和CRF受体。谷氨酸能投射到杏仁核的激活与应激反应有关。很少有研究评估神经递质刺激的杏仁核CRF释放。采用原代培养大鼠胚脑(E18-19)神经元的方法，观察了谷氨酸(0.1-1000 mU M)和N-甲基-D-天冬氨酸(NMDA，0.1-1000 mU M)对杏仁核CRF释放的影响。培养17-20天后进行实验。用放射免疫法测定CRF。兴奋性氨基酸神经递质谷氨酸和NMDA以浓度依赖的方式刺激CRF的释放。谷氨酸和NMDA的表观EC50值分别为17.5 mU M和12 mU M。谷氨酸刺激的CRF释放可被NMDA拮抗剂2-氨基-5-磷酸丙酸(AP-5，1-100 mU M)阻断，并可被1.2 mM的氯化镁拮抗。这些结果表明，抑制CRF在杏仁核的释放可能是NMDA拮抗剂抗焦虑作用的一个可能机制。(C)1999年，爱思唯尔科学公司。
Corticotropin-releasing factor (CRF) plays an important role in the activation of centrally mediated responses to stress. The amygdala, a limbic structure involved in the stress response, has a significant number of CRF cell bodies and CRF receptors. Activation of glutamatergic projections to the amygdala has been implicated in the stress response. Few studies have evaluated neurotransmitter-stimulated CRF release in the amygdala. We measured the effects of glutamate (0.1-1000 mu M) and N-methyl-D-aspartate (NMDA, 0.1-1000 mu M) on CRF release from the amygdala using primary neuronal cultures from embryonic rat brains (E18-19). Experiments were performed after the cultures grew for 17-20 days. CRF was measured using radioimmunoassay. The excitatory amino acid neurotransmitters, glutamate and NMDA, stimulated CRF release in a concentration-dependent manner. The apparent EC50 values for glutamate and NMDA were 17.5 mu M and 12 mu M, respectively. Consistent with a NMDA receptor-driven event, glutamate-stimulated CRF release was blocked by the NMDA antagonist, 2-amino-5-phosphonovaleric acid (AP-5, 1-100 mu M) and antagonized by the addition of 1.2 mM MgCl2 to the incubation medium. These results implicate an inhibition of CRF release in the amygdala as a possible mechanism for the reported anxiolytic effects of NMDA antagonists. (C) 1999 by Elsevier Science Inc.