EXCITATORY AMINO ACID RECEPTORS ARE COUPLED WITH PHOSPHOINOSITIDE METABOLISM

兴奋性氨基酸受体与磷酸肌醇代谢偶联

• 批准号: 4696429
• 负责人: F NICOLETTI
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF MENTAL HEALTH
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/4696429
• 关键词: aminophosphonate; anesthetics; aspartate; brain metabolism; butyrates; central nervous system; electrostimulus; glutamates; human tissue; inositol; lipid metabolism; mature animal; neurochemistry; phosphatidylinositols; phospholipids

We have shown for the first time that specific dicarboxylic amino acid recognition sites are coupled with inositol phospholipid metabolism in the rat central nervous system. These sites are abundant in the hippocampus, sensitive to the stimulatory action of ibotenic acid and are selectively antagonized by 2-amino-4-phosphonobutyric acid (APB). Glutamic and aspartic acids have marginal effect on inositol phospholipid metabolism in slices from adult animals but they markedly enhance inositol phospholipid hydrolysis (up to 15 fold) in slices from newborn animals. This action of glutamic acid declines progressively from the day 6th to the day 19th after the birth up to reach the adult levels on the day 30th after the birth. In the adult, the stimulatory action of dicarboxylic amino acids on inosidol phospholipid hydrolysis is potentiated following repeated electrical stimulation of limbic structures or after toxin-induced lesions of hippocampal excitatory pathways. We suggest that the stimulation of inositol phospholipid hydrolysis elicited by dicarboxylic amino acid may have a role in the cellular mechanism(s) underlying neuronal development as well as the regulation of limbic excitability.

我们首次证明了特定的二羧酸氨基酸 识别位点与肌醇磷脂代谢偶联， 大鼠中枢神经系统 这些部位在海马体中很丰富， 对鹅膏蕈氨酸的刺激作用敏感， 2-氨基-4-膦酰基丁酸（APB）可拮抗此作用。 谷氨酸和 天冬氨酸对肌醇磷脂代谢的影响很小， 但它们能显著增强肌醇磷脂 水解（高达15倍）在切片从新生动物。 的这个动作 谷氨酸从第6天到第19天逐渐下降， 出生后30天达到成年水平。 在成年人中，二羧酸氨基酸的刺激作用， 肌醇磷脂的水解作用在重复 边缘结构的电刺激或毒素诱导的损伤后 海马体兴奋性通路。 我们认为刺激肌醇磷脂水解 引起的二羧酸氨基酸可能有一个作用， 神经元发育的潜在机制以及 边缘系统兴奋性