Division of Neurology, Montreal General Hospital, 1650 Cedar Avenue, Montreal, P.O., Canada H3G 1A4.
J Neuroendocrinol. 1991 Oct 1;3(5):509-14. doi: 10.1111/j.1365-2826.1991.tb00311.x.
Abstract A considerable amount of evidence has accumulated to support a role for excitatory glutamatergic transmission in the regulation of the hypothalamo-neurohypophysial system. Glutamate immunoreactivity has been found in axon terminals forming asymmetric synapses on to magnocellular neurosecretory cells and kynurenic acid, a broad spectrum glutamate receptor antagonist inhibits 1) spontaneous electrical activity in vivo, 2) excitatory postsynaptic potentials in hypothalamic slices, and 3) osmotically-evoked vasopressin release from hypothalamic explants. While this provides strong evidence for glutamatergic regulation of hypothalamic magnocellular neurosecretory cells, the subtypes of glutamate receptors expressed by these cells have not been defined. We have, therefore, obtained current and voltage clamp recordings from supraoptic magnocellular neurosecretory cells in vitro to investigate the functional and pharmacological properties of their glutamate receptors. Application of micromolar concentrations of L-glutamate, or of the agonists kainate, quisqualate and N-methyl-D-aspartate (NMDA), produced reversible and dose-dependent depolarizations in all cells tested. These responses were mediated by postsynaptic receptors since they persisted during chemical synaptic blockade with Ca(2 +) -free or tetrodotoxin-containing solutions. The inward current induced by NMDA showed a marked Mg(2+)-sensitive voltage dependence, and was blocked by D, L-2-amino-5-phosphonovalerate. In contrast, currents induced by kainate and quisqualate showed linear current-voltage properties and were antagonized by 6-cyano-7-nitroquinoxaline-2,3-dione. We conclude that both NMDA and non-NMDA receptors are expressed by magnocellular neurosecretory cells of the rat supraoptic nucleus.
大量证据表明，兴奋性谷氨酸能传递在调节下丘脑-神经垂体系统中起重要作用。谷氨酸免疫反应性存在于形成与大细胞神经分泌细胞形成不对称突触的轴突末梢中，而广谱谷氨酸受体拮抗剂 kynurenic acid 可抑制 1）体内自发性电活动，2）下丘脑切片中的兴奋性突触后电位，以及 3）从下丘脑外植体中渗透诱发的血管加压素释放。虽然这为谷氨酸能调节下丘脑大细胞神经分泌细胞提供了强有力的证据，但这些细胞表达的谷氨酸受体亚型尚未确定。因此，我们已经从体外超视上核大细胞神经分泌细胞中获得了电流和电压钳记录，以研究其谷氨酸受体的功能和药理学特性。应用微摩尔浓度的 L-谷氨酸或激动剂 kainate、quisqualate 和 N-甲基-D-天冬氨酸 (NMDA)，可使所有测试细胞产生可逆且剂量依赖性的去极化。这些反应是由突触后受体介导的，因为它们在使用无 Ca2+或含河豚毒素的溶液进行化学突触阻断时仍然存在。NMDA 诱导的内向电流表现出明显的 Mg2+敏感电压依赖性，并且被 D，L-2-氨基-5-膦戊酸所阻断。相比之下，kainate 和 quisqualate 诱导的电流具有线性电流-电压特性，并且被 6-氰基-7-硝基喹喔啉-2,3-二酮所拮抗。我们得出结论，NMDA 和非 NMDA 受体均由大鼠视上核的大细胞神经分泌细胞表达。
