Nadler J V, Martin D, Bustos G A, Burke S P, Bowe M A
Department of Pharmacology, Duke University Medical Center, Durham, NC 27710.
Prog Brain Res. 1990;83:115-30. doi: 10.1016/s0079-6123(08)61245-5.
Excitatory synaptic transmission in the CNS can be modulated by endogenous substances and metabolic states that alter release of the transmitter, usually glutamate and/or aspartate. To explore this issue, we have studied the release of endogenous glutamate and aspartate from synaptic terminals of the CA3-derived Schaffer collateral, commissural and ipsilateral associational fibers in slices of hippocampal area CA1. These terminals release glutamate and aspartate in about a 5:1 ratio. The release process is modulated by adenosine, by the transmitters themselves and by nerve terminal metabolism. Adenosine inhibits the release of both amino acids by acting upon an A1 receptor. The transmitters, once released, can regulate their further release by acting upon both an NMDA and a non-NMDA (quisqualate/kainate) receptor. Activation of the NMDA receptor enhances the release of both glutamate and aspartate, whereas activation of the non-NMDA receptor depresses the release of aspartate only. Superfusion of CA1 slices with a glucose-deficient medium increases the release of both amino acids and reduces the glutamate/aspartate ratio. These results have implications for the regulation of excitatory synaptic transmission in the CA1 area and for the mechanism of hypoglycemic damage to CA1 pyramidal cells.
中枢神经系统中的兴奋性突触传递可被内源性物质和代谢状态所调节，这些物质和状态会改变递质的释放，通常是谷氨酸和/或天冬氨酸。为了探究这个问题，我们研究了海马体CA1区切片中源自CA3的谢弗侧支、连合纤维和同侧联合纤维的突触终末释放内源性谷氨酸和天冬氨酸的情况。这些终末以大约5:1的比例释放谷氨酸和天冬氨酸。释放过程受腺苷、递质自身以及神经终末代谢的调节。腺苷通过作用于A1受体来抑制这两种氨基酸的释放。递质一旦释放，可通过作用于NMDA受体和非NMDA（quisqualate/海人藻酸）受体来调节其进一步释放。NMDA受体的激活增强谷氨酸和天冬氨酸的释放，而非NMDA受体的激活仅抑制天冬氨酸的释放。用缺乏葡萄糖的培养基灌注CA1区切片会增加这两种氨基酸的释放并降低谷氨酸/天冬氨酸的比例。这些结果对CA1区兴奋性突触传递的调节以及CA1锥体细胞低血糖损伤的机制具有启示意义。
