The neuropharmacological study of endogenous glutamate release from the stomach

胃内源性谷氨酸释放的神经药理学研究

• 批准号: 08670114
• 负责人: OKUMA Yasunobu
• 金额: $ 0.96万
• 依托单位: HOKKAIDO UNIVERSITY (1997)Kochi Medical School (1996)
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1996
• 资助国家: 日本
• 起止时间: 1996 至 1997
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08670114/
• 关键词: stomach; glumatane release; KCI stimulation; vagus nerve stimulation; calcium channels; omega-agatoxin IVA; isradipine; KCl刺激; グルタミン酸; ω-Agatoxin IVA

To investigate a possible physiological role of glutamate in the stomach, release of endogenous glutamate from an isolated vascularly perfused rat stomach preparation was studied. Glutamate was measured by bioluminescence assay method.High concentration of KCI (30-75mM) induced a dose dependent release of glutamate. This KCI-induced release of glutamate was abolished in calcium-free medium containing EGTA.Electrical stimulation of the vagus nerves also induced a release of glutamate. This vagal stimulation-induced release of glutamate was abolished by both calcium removal and tetrodotoxin (TTX). Amounts of other 13 amino acids in the medium, detectable by the automatic amino acid analyzer, were not significantly affected by both high-K+and the vagal stimulation.In the next series, we examined properties of calcium channel subtypes mediating.endogenous glutamate release from the stomach. The 50 mM KCI elicited release of glutamate was significantly inhibited by both omega-agatoxin IVA,a P/Q-type calcium channel antagonist, and isradipine, an L type calcium channel antagonist. Omega-Conotoxin GVIA,an N type calcium channel antagonist and flunarizine, a nonselective T-type calcium channel antagonist were without effect. In contrast to this case of glutamate, omega-conotoxin GVIA induced a marked inhibition in the release of gastric noradrenaline. The combined treatment with omega-agatoxin IVA plus isradipine produced a marked synergistic inhibition of the glutamate release. This inhibition was, however, much less than that by cadmium. These results provide an additional evidence that glutamate probably serves as a neurotransmitter in the stomach, and suggest that P/Q and L type calcium channels coexist to regulate the release of gastric glutamate. Furthermore, it is possible that unidentified calcium channels other than P/Q and L type channels are also involved in the release of glutamate in the stomach.

为了研究谷氨酸在胃中可能的生理作用，研究了从离体血管灌注的大鼠胃制备物释放内源性谷氨酸。用生物发光法测定谷氨酸的含量，高浓度KCl（30- 75 mM）诱导谷氨酸的释放，并呈剂量依赖性。在含EGTA的无钙培养基中，KCl诱导的谷氨酸释放被消除。电刺激迷走神经也诱导谷氨酸释放。这种迷走神经刺激诱导的谷氨酸释放被取消钙去除和河豚毒素（TTX）。培养基中其他13种氨基酸的量，可通过自动氨基酸分析仪检测，不受高K+和迷走神经刺激的显著影响。在接下来的系列中，我们研究了钙通道亚型介导的特性。内源性谷氨酸从胃中释放。50 mM KCl引起的谷氨酸释放被P/Q型钙通道拮抗剂ω-agatoxin IVA和L型钙通道拮抗剂伊拉地平显著抑制。N型钙通道拮抗剂ω-芋螺毒素GVIA和非选择性T型钙通道拮抗剂氟桂利嗪均无作用。与谷氨酸盐的这种情况相反，ω-芋螺毒素GVIA诱导胃去甲肾上腺素释放的显着抑制。与ω-agatoxin IVA加伊拉地平的组合治疗产生了显着的协同抑制谷氨酸的释放。然而，这种抑制作用远小于镉。这些结果为谷氨酸可能作为胃内的一种神经递质提供了又一证据，并提示P/Q和L型钙通道共存调节胃谷氨酸的释放。此外，除了P/Q和L型通道之外，可能还存在未鉴定的钙通道参与胃中谷氨酸的释放。

项目成果

Okuma, Y.et al: "Calcium-dependent release of endogenous glutamate from vascularly perfused rat stomach in vitro." J Neuroscince Research. 44・5. 507-511 (1996)

Okuma, Y. 等人：“体外血管灌注的大鼠胃中钙依赖性释放”，J Neuroscience Research 44·5 (1996)。

Murakami,Y.et al: "Nitric oxide mediates central activation of sympathetic outflow induced by interleukin-1β in rats.Eur.J.Pharmacol." Eur.J.Pharmacol.317. 61-66 (1996)

Murakami, Y. 等人：“一氧化氮介导白介素 1β 诱导的大鼠交感神经流出的中枢激活。Eur.J.Pharmacol.317 (1996)。”

Okuma, Y.et al: "Brain prostaglandins mediate the bombesin-induced increase in plasma levels of catecholamines." Life Sciences. 59. 1217-1225 (1996)

Okuma, Y.等人：“脑前列腺素介导铃蟾肽诱导的儿茶酚胺血浆水平增加。”

大熊康修: "脳虚血へのグリア細胞のサイトカイン,ケモカイン,iNOS誘導応答とニューロン死" 日本薬理学雑誌, 8 (1998)

Yasunori Okuma：“细胞因子、趋化因子和 iNOS 诱导的神经胶质细胞对脑缺血和神经元死亡的反应”《日本药理学杂志》，8 (1998)

Okuma, Y.et al: "Calcium-dependent release of endogenous glutamate from vascularly perfused rat stomach in vitro." J Neuroscience Research. 44・5. 507-511 (1996)

Okuma, Y. 等人：“体外血管灌注的大鼠胃中钙依赖性释放”，J Neuroscience Research 44·5 (1996)。