Bagosi Zsolt, Jászberényi Miklós, Szabó Gyula, Telegdy Gyula
Department of Pathophysiology, University of Szeged, H-6701 Szeged, Semmelweis u. 1., PO Box 427, Hungary.
Brain Res Bull. 2008 Jan 31;75(1):15-7. doi: 10.1016/j.brainresbull.2007.07.003. Epub 2007 Jul 26.
Corticotropin-releasing factor (CRF) is the major neuromodulator of the hypothalamic-pituitary-adrenal axis, regulating the behavioural, endocrine, autonomic and immune responses to stress. Together with the recently discovered members of the CRF peptide family, urocortin 1, urocortin 2 and urocortin 3, it also has neurotransmitter actions. Previous publication has demonstrated that stress induces CRF release in the paraventricular nucleus of the hypothalamus and the release of both CRF and GABA in the amygdala. Accordingly, the aim of the present study was to determine the effects of the members of the CRF peptide family on GABA release from the amygdala by using an in vitro superfusion system. In order to study the participation of different CRF receptors (CRF1 and CRF2) in this process, rat amygdalar slices were pretreated with selective CRF1 and CRF2 antagonists. CRF and urocortin 1 significantly increased the release of [(3)H]GABA from the slices following electrical stimulation, whereas urocortin 2 and urocortin 3 were ineffective. The actions of CRF and urocortin 1 were blocked by the selective CRF1 receptor antagonist antalarmin, but were not inhibited by the selective CRF2 receptor antagonist astressin 2B, both administered in equimolar doses. Our results demonstrate that the release of GABA from the amygdala is mediated by CRF and urocortin 1 through the activation of CRF1 receptors.
促肾上腺皮质激素释放因子（CRF）是下丘脑 - 垂体 - 肾上腺轴的主要神经调节因子，调节对应激的行为、内分泌、自主神经和免疫反应。它与最近发现的CRF肽家族成员，即尿皮质素1、尿皮质素2和尿皮质素3一起，还具有神经递质作用。先前的研究表明，应激可诱导下丘脑室旁核中CRF的释放以及杏仁核中CRF和γ-氨基丁酸（GABA）的释放。因此，本研究的目的是通过体外灌流系统确定CRF肽家族成员对杏仁核中GABA释放的影响。为了研究不同的CRF受体（CRF1和CRF2）在此过程中的参与情况，用选择性CRF1和CRF2拮抗剂预处理大鼠杏仁核切片。电刺激后，CRF和尿皮质素1显著增加了切片中[³H]GABA的释放，而尿皮质素2和尿皮质素3则无效。CRF和尿皮质素1的作用被等摩尔剂量给予的选择性CRF1受体拮抗剂安他乐明阻断，但未被选择性CRF2受体拮抗剂阿斯特辛2B抑制。我们的结果表明，杏仁核中GABA的释放是由CRF和尿皮质素1通过激活CRF1受体介导的。
