COEXISTENCE OF CARRIERS FOR DOPAMINE AND GABA UPTAKE ON A SAME NERVE-TERMINAL IN THE RAT-BRAIN

COEXISTENCE OF CARRIERS FOR DOPAMINE AND GABA UPTAKE ON A SAME NERVE-TERMINAL IN THE RAT-BRAIN
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DOI:
10.1111/j.1476-5381.1987.tb09004.x
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发表时间:
1987-05-01
影响因子:
7.3
通讯作者:
RAITERI, M
RAITERI, M
中科院分区:
医学2区
文献类型:
--
作者:
BONANNO, G;RAITERI, M

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1 检查了γ-氨基丁酸(GABA)影响大鼠脑突触体中[3H]-多巴胺释放的能力,所述突触体由纹状体、额叶皮层和下丘脑制备并在地昔帕明存在下用放射性儿茶酚胺预先标记。 2 GABA (10-300 μM) 以浓度依赖性方式增加纹状体和皮质突触体的 [3H]-多巴胺的基础释放;然而,它对下丘脑神经末梢的影响不太明显。 2,4-二氨基丁酸 (DABA) 模仿 GABA,但效力较弱。 3 中性氨基酸例如亮氨酸、缬氨酸或α-氨基异丁酸(100-300μM)不影响或最小程度地增加[3H]-多巴胺的释放。 4 GABAA 受体拮抗剂荷包牡丹碱或印防己毒素不能阻止 GABA 诱导的 [3H]-多巴胺释放。 GABAA-受体激动剂,蝇蕈醇(10-300μM)仅表现出对[3H]-多巴胺释放的非常弱的、不显着的增强作用。 GABAB-受体激动剂(-)-巴氯芬(100或300μM)没有效果。 5 三种新型选择性 GABA 摄取抑制剂:N-(4,4-二苯基-3-丁烯基)-哌啶酸 (SK 和 F 89976A)、N-(4,4-二苯基-3-丁烯基)-番石榴碱 (SK 和 F 100330A) 和 N-(4,4-二苯基-3-丁烯基)-高-β-脯氨酸 (SK 和 F) 100561) 有效抵消 GABA 对 [3H]-多巴胺释放的增强作用。哌啶酸也降低 GABA 的作用。 6 结论是,摄取多巴胺和 GABA 的载体可能共存于大鼠大脑的同一神经末梢上。
1 The ability of .gamma.-aminobutyric acid (GABA) to affect the release of [3H]-dopamine in rat brain synaptosomes prepared from corpus striatum, frontal cortex and hypothalamus and prelabelled with the radioactive catecholamine in the presence of desipramine was examined. 2 GABA (10-300 .mu.M) increased in a concentration-dependent way the basal release of [3H]-dopamine from striatum and cortical synaptosomes; however, its effect was much less pronounced in hypothalamic nerve terminals. 2,4-Diaminobutyric acid (DABA) mimicked GABA although less potently. 3 Neutral amino acids such as leucine, valine or .alpha.-aminoisobutyric acid (100-300 .mu.M) did not affect or increased minimally the release of [3H]-dopamine. 4 The GABA-induced [3H]-dopamine release was not prevented by the GABAA-receptor antagonists, bicuculline or picrotoxin. The GABAA-receptor agonist, muscimol (10-300 .mu.M), displayed only a very weak, not significant, enhancing effect on [3H]-dopamine release. The GABAB-receptor agonist (-)-baclofen (100 or 300 .mu.M) had no effect. 5 Three novel and selective inhibitors of GABA uptake, N-(4,4-diphenyl-3-butenyl)-nipecotic acid (SK and F 89976A), N-(4,4-diphenyl-3-butenyl)-guvacine (SK and F 100330A) and N-(4,4-diphenyl-3-butenyl)-homo-.beta.-proline (SK and F 100561) potently counteracted the enhancing effect of GABA on [3H]-dopamine release. Nipecotic acid also reduced the effect of GABA. 6 It is concluded that carriers for the uptake of dopamine and GABA may coexist on the same nerve terminal in the rat brain.