L-GLUTAMATE-EVOKED RELEASE OF DOPAMINE FROM SYNAPTOSOMES OF THE RAT STRIATUM - INVOLVEMENT OF AMPA AND N-METHYL-D-ASPARTATE RECEPTORS
L-GLUTAMATE-EVOKED RELEASE OF DOPAMINE FROM SYNAPTOSOMES OF THE RAT STRIATUM - INVOLVEMENT OF AMPA AND N-METHYL-D-ASPARTATE RECEPTORS
复制标题
DOI：
10.1016/0306-4522(92)90249-2
复制
发表时间：
1992-03-01
期刊：
影响因子：
3.3
通讯作者：
GLOWINSKI, J
中科院分区：
文献类型：
--
作者：
DESCE, JM;GODEHEU, G;GLOWINSKI, J
以前，使用纯化的大鼠纹状体突触体，我们已经表明，D，L-α-氨基-3-羟基-5-甲基-4-异恶唑丙酸酯（AMPA）受体的激动剂刺激释放[H-3]多巴胺连续合成[H-3]酪氨酸，类似的结果与N-甲基-D-天冬氨酸在镁的情况下获得。在本研究中，使用相同的方法，试图确定是否在镁的存在下，AMPA受体的联合刺激使我们能够证明突触前促进[H-3]多巴胺释放通过N-甲基-D-天冬氨酸受体。L-谷氨酸（10（-3）M）显著刺激突触体释放[H-3]多巴胺，这种作用约为AMPA（10（-3）M）的两倍，而N-甲基-D-天冬氨酸（10（-3）M）即使在甘氨酸（10（-6）M）存在下也无效。与先前的结果一致，仅在不存在镁的情况下观察到N-甲基-D-天冬氨酸和甘氨酸的刺激作用。这种反应被6，7-二硝基-喹喔啉-2，3-二酮（3 × 10（-5）M）阻断，证实了通常用作AMPA拮抗剂的该化合物也阻断N-甲基-D-天冬氨酸受体。在士的宁存在下，联合应用N-甲基-D-天冬氨酸（10（-3）M）和甘氨酸（10（-6）M）可显著增强AMPA（10（-3）M）诱发的[H-3]多巴胺释放，表明AMPA受体的同时激活消除了N-甲基-D-天冬氨酸受体的电压依赖性镁阻滞。甘氨酸（10（-6）M）可增强L-谷氨酸（10（-3）M）诱发的[H-3]多巴胺释放。仅部分被（+）-5-甲基-10，11-二氢-5H-二苯并（a，d）环庚烯-5，1-亚胺马来酸盐（MK 801）（10（-5）M）还原，几乎完全被6，7-二硝基-喹喔啉-2，3-二酮（3 x 10（-5）M）消除。另外。L-谷氨酸（10（-3）M）诱发的[H-3]多巴胺释放在有或无镁的情况下具有相似的幅度。这些结果表明，L-谷氨酸在高浓度下。通过作用于AMPA和N-甲基-D-天冬氨酸受体，促进[H-3]多巴胺从大鼠纹状体突触体的释放，即使在镁的存在下。
Previously, using purified synaptosomes from the rat striatum, we have shown that agonists of D,L-alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) receptors stimulate the release of [H-3]dopamine continuously synthesized from [H-3]tyrosine, Similar results were obtained with N-methyl-D-aspartate in the absence of magnesium. In the present study, using the same approach, attempts were made to determine whether in the presence of magnesium, the combined stimulation of AMPA receptors allows us to demonstrate the presynaptic facilitation of [H-3]dopamine release through N-methyl-D-aspartate receptors. L-Glutamate (10(-3) M) markedly stimulated the release of [H-3]dopamine from synaptosomes, this effect being about twice that found with AMPA (10(-3) M) while N-methyl-D-aspartate (10(-3) M) even in the presence of glycine (10(-6) M) was ineffective. In agreement with previous results, a stimulatory effect of N-methyl-D-aspartate and glycine was only observed in the absence of magnesium. This response was blocked by 6,7-dinitro-quinoxaline-2,3-dione (3 x 10(-5) M), confirming that this compound, generally used as an AMPA antagonist, also blocks N-methyl-D-aspartate receptors. The AMPA (10(-3) M)-evoked release of [H-3]dopamine was markedly potentiated by the combined application of N-methyl-D-aspartate (10(-3) M) and glycine (10(-6) M) in the presence of strychnine, indicating that the concomitant activation of AMPA receptors removes the voltage-dependent magnesium block of N-methyl-D-aspartate receptors. The L-glutamate (10(-3) M)-evoked release of [H-3]dopamine was potentiated by glycine (10(-6) M). only partially reduced by (+)-5-methyl-10,11-dihydro-5H-dibenzo(a,d)cyclohepten-5,1-imine maleate (MK801) (10(-5) M) and almost completely abolished by 6,7-dinitro-quinoxaline-2,3-dione (3 x 10(-5) M). In addition. the L-glutamate (10(-3) M)-evoked release of [H-3]dopamine was of similar amplitude in either the presence or absence of magnesium.Altogether. these results demonstrate that L-glutamate, in high concentration. facilitates the release of [H-3]dopamine from rat striatal synaptosomes by acting both on AMPA and N-methyl-D-aspartate receptors, even in the presence of magnesium.