RELEASE OF ADENOSINE BY ACTIVATION OF NMDA RECEPTORS IN THE HIPPOCAMPUS
RELEASE OF ADENOSINE BY ACTIVATION OF NMDA RECEPTORS IN THE HIPPOCAMPUS
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DOI：
10.1126/science.7916485
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发表时间：
1994-09-30
期刊：
影响因子：
56.9
通讯作者：
NICOLL, RA
中科院分区：
文献类型：
--
作者：
MANZONI, OJ;MANABE, T;NICOLL, RA
腺苷大量存在于哺乳动物脑中，对神经元活动有明显影响，但其在神经信号传导中的作用知之甚少。谷氨酸受体激动剂N-甲基-D-天冬氨酸（NMDA）引起豚鼠海马脑片CA 1区兴奋性突触传递的突触前抑制。这种抑郁症被腺苷A1受体拮抗剂阻断，这表明谷氨酸受体的NMDA亚型的激活提高了细胞外腺苷的浓度，其作用于突触前抑制性A1受体。强强直刺激引起的异突触抑制，这是由NMDA和A1受体拮抗剂阻断。选择性抑制中间神经元的脑啡肽拮抗异突触抑制。这些发现表明，突触释放的谷氨酸激活NMDA受体，这反过来释放腺苷，至少部分从中间神经元，在一定距离处起作用，以抑制突触前从兴奋性突触释放谷氨酸。因此，中间神经元可能介导广泛的嘌呤能突触前抑制。
Adenosine is present in the mammalian brain in large amounts and has patent effects on neuronal activity, but its role in neural signaling is poorly understood. The glutamate receptor agonist N-methyl-D-aspartate (NMDA) caused a presynaptic depression of excitatory synaptic transmission in the CA1 region of guinea pig hippocampal slices. This depression was blocked by an adenosine A1 receptor antagonist, which suggests that activation of the NMDA subtype of glutamate receptor raises the concentration of extracellular adenosine, which acts on presynaptic inhibitory A1 receptors. Strong tetanic stimulation caused a heterosynaptic inhibition that was blocked by both NMDA and A1 receptor antagonists. Enkephalin, which selectively inhibits interneurons, antagonized the heterosynaptic inhibition. These findings suggest that synaptically released glutamate activates NMDA receptors, which in turn releases adenosine, at least in part from interneurons, that acts at a distance to inhibit presynaptically the release of glutamate from excitatory synapses. Thus, interneurons may mediate a widespread purinergic presynaptic inhibition.