Presynaptically mediated effects of cholecystokinin-8 on the excitability of area postrema neurons in rat brain slices.
Presynaptically mediated effects of cholecystokinin-8 on the excitability of area postrema neurons in rat brain slices.
复制标题
胆囊收缩素 8 对大鼠脑切片后区神经元兴奋性的突触前介导作用。
DOI：
10.1016/j.brainres.2015.05.018
复制
发表时间：
2015
期刊：
影响因子：
2.9
通讯作者：
Funahashi M
中科院分区：
文献类型：
--
作者：
Sugeta S;Hirai Y;Maezawa H;Inoue N;Yamazaki Y;Funahashi M
胆囊收缩素 (CCK) 是一种众所周知的肠道激素，通过作用于外周和中枢受体而显示出抑制食欲的作用。 CCK 也广泛分布在整个哺乳动物大脑中，似乎具有神经递质和神经调节剂的功能。后区是室周器官之一，位于第四脑室尾端延髓的背侧表面。后区的血管缺乏血脑屏障，为特定的中枢神经元件提供了独特的接触循环物质的通道。免疫组织化学研究显示后区存在 CCK-A 受体，我们报道了 CCK 敏感区后区神经元。然而，CCK 在后区神经元中的感受机制仍不清楚。我们使用大鼠脑切片中的全细胞和穿孔膜片钳记录研究了后区神经元对 CCK 受体激动剂和拮抗剂的反应。 CCK-8 的应用引发了兴奋性反应，例如 mEPSC（微型兴奋性突触后电流）频率增加、mEPSC 振幅增大以及动作电位频率增加。这些变化主要出现在不显示超极化激活阳离子电流 (Ih) 的细胞中，除了少数 Ih 阳性神经元中的微小兴奋性变化外。从未见过强直内向电流或对 CCK-8 的抑制反应。对 CCK-8 给药前后 mEPSC 振幅的分析表明，反应是通过突触前受体介导的。当 CNQX（AMPA 型谷氨酸受体拮抗剂）存在时，CCK-8 的作用被消除。在洛格鲁胺（一种选择性 CCK-A 受体拮抗剂）存在的情况下，CCK-8 诱导的兴奋反应被抑制。没有细胞对非硫酸化 CCK-8（CCK-8NS，一种选择性 CCK-B 受体激动剂）的给药产生反应。我们得出结论，CCK-8 通过突触前 CCK-A 受体发挥其作用，促进谷氨酸释放到 Ih 阴性区域后细胞上。
Cholecystokinin (CCK) is a well-known gut hormone that shows anorexigenic effects via action at peripheral and central receptors. CCK is also widely distributed throughout the mammalian brain and appears to function as a neurotransmitter and neuromodulator. The area postrema is one of the circumventricular organs, located on the dorsal surface of the medulla oblongata at the caudal end of the fourth ventricle. Blood vessels in the area postrema lack a blood brain barrier, offering specific central neural elements unique access to circulating substances. Immunohistochemical studies show CCK-A receptors in the area postrema, and we reported CCK-sensitive area postrema neurons. However, the receptive mechanism of CCK in area postrema neurons still remains unexplained. We investigated the responses of area postrema neurons to agonists and antagonists of CCK receptors using whole cell and perforated patch-clamp recordings in rat brain slices. The application of CCK-8 elicited excitatory responses, such as increases in the frequency of mEPSCs (miniature excitatory postsynaptic currents), a shift toward larger amplitude mEPSCs, and increases in the frequency of action potentials. These changes were found mostly in cells not displaying the hyperpolarization-activated cation current (Ih), except for small excitatory changes in a minority of Ih-positive neurons. Tonic inward currents or an inhibitory response to CCK-8 were never seen. Analysis of the amplitude of mEPSCs before and after the administration of CCK-8 indicated the responses mediated via the presynaptic receptors. The effect of CCK-8 was abolished in the presence of CNQX (AMPA type glutamate receptor antagonist). In the presence of lorglumide (a selective CCK-A receptor antagonist), CCK-8-induced excitatory responses were inhibited. No cells responded to the administration of non-sulfated CCK-8 (CCK-8NS, a selective CCK-B receptor agonist). We conclude that CCK-8 exerts its action via presynaptic CCK-A receptors to facilitate glutamate release onto Ih-negative area postrema cells.