Department of Molecular Neuroscience, UCL Institute of Neurology, Queen Square, London WC1N 3BG, UK.
Cell Death Dis. 2013 Jan 10;4(1):e455. doi: 10.1038/cddis.2012.194.
Glutamate excitotoxicity is responsible for neuronal death in acute neurological disorders including stroke, trauma and neurodegenerative disease. Loss of calcium homeostasis is a key mediator of glutamate-induced cell death. The neurotransmitter dopamine (DA) is known to modulate calcium signalling, and here we show that it can do so in response to physiological concentrations of glutamate. Furthermore, DA is able to protect neurons from glutamate-induced cell death at pathological concentrations of glutamate. We demonstrate that DA has a novel role in preventing delayed calcium deregulation in cortical, hippocampal and midbrain neurons. The effect of DA in abolishing glutamate excitotoxicity can be induced by DA receptor agonists, and is abolished by DA receptor antagonists. Our data indicate that the modulation of glutamate excitotoxicity by DA is receptor-mediated. We postulate that DA has a major physiological function as a safety catch to restrict the glutamate-induced calcium signal, and thereby prevent glutamate-induced cell death in the brain.
谷氨酸兴奋性毒性是导致急性神经紊乱（包括中风、创伤和神经退行性疾病）神经元死亡的原因。钙稳态失衡是谷氨酸诱导细胞死亡的关键介质。神经递质多巴胺（DA）已知可调节钙信号，而我们在这里显示它可以响应生理浓度的谷氨酸做出反应。此外，DA 能够在病理浓度的谷氨酸下保护神经元免受谷氨酸诱导的细胞死亡。我们证明 DA 在预防皮质、海马和中脑神经元中延迟的钙失调方面具有新的作用。DA 通过 DA 受体激动剂消除谷氨酸兴奋性毒性的作用可以被 DA 受体拮抗剂所消除。我们的数据表明，DA 通过受体介导来调节谷氨酸兴奋性毒性。我们推测 DA 作为一个主要的生理功能，作为安全装置来限制谷氨酸诱导的钙信号，从而防止大脑中谷氨酸诱导的细胞死亡。
