Bowyer J F, Newport G D, Lipe G W, Frame L T
Division of Neurotoxicology, National Center for Toxicological Research, Jefferson, Arkansas.
J Pharmacol Exp Ther. 1992 Apr;261(1):72-80.
Exogenous glutamate will evoke dopamine (DA) release from striatal slices in vitro. To further characterize glutamate-evoked DA release from striatal slices, experiments were designed to: 1) determine if sufficient endogenous glutamate can be released in vitro to presynaptically mediate [3H]DA release in the absence of Mg++ and 2) reevaluate how K+ depolarization affects glutamate-evoked [3H]DA release. Removal of Mg++ to potentiate N-methyl-D-aspartate (NMDA) receptor-mediated DA release increased 15 mM K(+)-evoked [3H]DA release to about 200% of control. The potentiation of this release was probably not mediated by NMDA receptors because it was not blocked by the glutamate receptor antagonists MK-801, 6,7-dinitroquinoxalinedione (DNQX) or kynurenate. Furthermore, the removal of Mg++ increased DA release substantially (200%) in the presence of 5 microM sulpiride and 10 microM nomifensine, indicating that DA reuptake and DA D2 autoreceptors are not primarily responsible for increased DA release. In the absence of Mg++, depolarization produced by 20 mM or greater [K+] inhibited DA released by exogenous glutamate, whereas a much higher [K+] was necessary to evoke endogenous glutamate release. In the presence of 1.5 mM Mg++, a reduction of the "Mg++ blockade" of NMDA receptors by 15 mM K+ depolarization during glutamate-evoked DA release was evaluated with and without the DA reuptake inhibitor nomifensine and the DA D2 antagonist sulpiride. DA released by K+ depolarization (Mg++ present) was markedly increased by 1 mM glutamate, but this effect was only partially reversed by kynurenate or high concentrations of either MK-801 (25 microM) or DNQX (100 microM).(ABSTRACT TRUNCATED AT 250 WORDS)
外源性谷氨酸会在体外诱发纹状体切片释放多巴胺（DA）。为了进一步明确谷氨酸诱发纹状体切片释放DA的特性，设计了如下实验：1）确定在无Mg++的情况下，体外能否释放足够的内源性谷氨酸以突触前介导[3H]DA释放；2）重新评估K+去极化如何影响谷氨酸诱发的[3H]DA释放。去除Mg++以增强N-甲基-D-天冬氨酸（NMDA）受体介导的DA释放，可使15 mM K+诱发的[3H]DA释放增加至对照的约200%。这种释放增强可能并非由NMDA受体介导，因为它未被谷氨酸受体拮抗剂MK-801、6,7-二硝基喹喔啉二酮（DNQX）或犬尿烯酸阻断。此外，在存在5 μM舒必利和10 μM诺米芬辛的情况下，去除Mg++可使DA释放大幅增加（200%），表明DA再摄取和DA D2自身受体并非DA释放增加的主要原因。在无Mg++时，20 mM或更高浓度的[K+]产生的去极化会抑制外源性谷氨酸释放的DA，而诱发内源性谷氨酸释放则需要更高浓度的[K+]。在存在1.5 mM Mg++的情况下，在有和没有DA再摄取抑制剂诺米芬辛及DA D2拮抗剂舒必利的条件下，评估了谷氨酸诱发DA释放期间15 mM K+去极化对NMDA受体“Mg++阻断”的减弱作用。K+去极化（存在Mg++）释放的DA在加入1 mM谷氨酸后显著增加，但这种作用仅被犬尿烯酸或高浓度的MK-801（25 μM）或DNQX（100 μM）部分逆转。（摘要截短于250字）
