Influence of dopamine on GABA release in striatum: Evidence for D-1-D-2 interactions and non-synaptic influences
Influence of dopamine on GABA release in striatum: Evidence for D-1-D-2 interactions and non-synaptic influences
复制标题
DOI：
10.1016/s0306-4522(96)00475-7
复制
发表时间：
1997-03-01
期刊：
影响因子：
3.3
通讯作者：
Zigmond, MJ
中科院分区：
文献类型：
--
作者：
Harsing, LG;Zigmond, MJ
将大鼠纹状体切片与 [H-3]GABA 预孵育，并在哌啶酸和氨氧乙酸（分别是高亲和力 GABA 转运抑制剂和 GABA 转氨酶抑制剂）存在下进行灌注。 GABA 外流通过监测氚外流来估算，其中 98% 为 [H-3]GABA 形式。进行了以下三个主要观察：（1）SKF-38393（10μM）（多巴胺受体 D-1 家族的激动剂）使电场刺激（8 Hz）引起的 GABA 溢出增加两倍。这种增加被 D-1 受体拮抗剂 SCH-23390 (10 μM) 完全阻断。然而，单独给予 SCH-23390 对 GABA 溢出没有影响。因此，多巴胺激动剂似乎对 GABA 释放产生兴奋性影响；然而，在本实验条件下，内源性多巴胺并未引起这种效应。 (2) 喹吡罗 (10 μM)（多巴胺受体 D-2 家族的激动剂）可将电诱发的 GABA 溢出降低 50%，而这种作用可被 D-2 拮抗剂舒必利 (10 μM) 阻断。此外，单独接触舒必利会导致 GABA 溢出增加 60%，这种效应被多巴胺合成抑制剂 3-碘酪氨酸 (2 mM) 消除。因此，D-2激动剂似乎对多巴胺释放产生抑制作用，这种作用可以通过内源性多巴胺储存来发挥。 (3) SKF-38393 的刺激作用被喹吡罗减弱，而舒必利诱导的 GABA 流出增加被 SCH-23390 减弱。舒必利还在 KCl 诱导的去极化过程中增加 [H-3]GABA 流出，这种效应在电刺激的情况下被 SCH-23390 拮抗。然而，虽然河豚毒素不会改变舒必利的刺激作用，但它确实阻断了 SCH-23390 拮抗舒必利诱导的 GABA 溢出增加的能力。后者的结果表明，D-1 和 D-2 受体之间存在相互作用，通过 D-1 位点介导的多巴胺作用被 D-2 位点的作用所抑制。总之，我们的结果表明（i）多巴胺激动剂可以通过 D-1 受体对新纹状体内去极化诱导的 GABA 释放产生兴奋性影响，并通过 D-2 受体产生抑制性影响； (ii)在这些实验的条件下，内源性多巴胺不能作用于D-1位点，但确实通过D-2位点发挥抑制影响：并且(iii)D-1和D-2受体之间存在相互作用，使得通过D-1位点介导的多巴胺的作用由于通过D-2位点施加的伴随作用而受到抑制。 (C) 1997 国际广播组织。
Striatal slices from the rat were preincubated with [H-3]GABA and superfused in the presence of nipecotic acid and aminooxyacetic acid, inhibitors of high-affinity GABA transport and GABA aminotransferase, respectively. GABA efflux was estimated by monitoring tritium efflux, 98% of which was in the form of [H-3]GABA. The following three major observations were made: (1) The overflow of GABA evoked by electrical field stimulation (8 Hz) was increased two-fold by SKF-38393 (10 mu M), an agonist at the D-1 family of dopamine receptors. This increase was completely blocked by the D-1 receptor antagonist SCH-23390 (10 mu M). However, SCH-23390 had no effect on GABA overflow when given alone. Thus, dopamine agonists appear to exert an excitatory influence on GABA release; however, this effect was not elicited by endogenous dopamine under the conditions of this experiment. (2) Electrically evoked GABA overflow was reduced 50%, by quinpirole (10 mu M), an agonist at the D-2 family of dopamine receptors, and this effect was blocked by the D-2 antagonist sulpiride (10 mu M). Moreover, exposure to sulpiride alone caused a 60% increase in GABA overflow, and this effect was abolished by 3-iodotyrosine (2 mM), a dopamine synthesis inhibitor. Thus, D-2 agonists appear to exert an inhibitory influence on dopamine release, an effect that can be exerted by endogenous stores of dopamine. (3) The stimulatory effect of SKF-38393 was attenuated by quinpirole, whereas the sulpiride-induced increase in GABA efflux was attenuated by SCH-23390. Sulpiride also increased [H-3]GABA efflux during KCl-induced depolarization, an effect that was antagonized by SCH-23390 as in the case of electrical stimulation. However, although tetrodotoxin did not alter the stimulatory effect of sulpiride, it did block the ability of SCH-23390 to antagonize the sulpiride-induced increase in GABA overflow. These latter results suggest that there is an interaction between D-1 and D-2 receptors whereby the effects of dopamine mediated via D-1 sites are inhibited by an action on D-2 sites.In conclusion, our results suggest that (i) dopamine agonists can exert an excitatory influence on depolarization-induced GABA release within neostriatum via D-1 receptors and an inhibitory influence via D-2 receptors; (ii) under the conditions of these experiments, endogenous dopamine fails to act on D-1 sites but does exert an inhibitory influence via D-2 sites: and (iii) there is an interaction between D-1 and D-2 receptors such that the actions of dopamine mediated via D-1 sites are inhibited as a result of the concomitant actions exerted via D-2 sites. (C) 1997 IBRO.