Characterization of nicotinic agonist-induced [3H] dopamine release from synaptosomes prepared from four mouse brain regions
Characterization of nicotinic agonist-induced [3H] dopamine release from synaptosomes prepared from four mouse brain regions
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DOI：
10.1124/jpet.301.2.651
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发表时间：
2002-05-01
影响因子：
3.5
通讯作者：
Collins, AC
中科院分区：
文献类型：
--
作者：
Grady, SR;Murphy, KL;Collins, AC
研究了对从四个小鼠大脑区域制备的突触体摄取[H-3]多巴胺的抑制。抑制曲线表明，在纹状体、伏隔核和嗅结节三个区域中，[H-3]多巴胺仅被多巴胺能末端吸收。然而，在额叶皮层中，只有一部分吸收进入多巴胺能末梢，其中较大部分被去甲肾上腺素能末梢吸收，另一小部分被血清素能末梢吸收。额叶皮层的释放研究表明，在该区域中，只有多巴胺能和去甲肾上腺素能末端能够以允许囊泡介导释放的形式包装[H-3]多巴胺；此外，只有多巴胺能末端具有功能性突触前 nAChR，当受到烟碱激动剂刺激时，会引起 [H-3] 多巴胺释放。激动剂刺激的[H-3]多巴胺释放通过四个小鼠大脑区域制备的突触体进行表征。 α-芋螺毒素 MII 是所有脑区多巴胺释放的部分抑制剂，这表明所有四个脑区的神经末梢至少表达两种烟碱胆碱能受体 (nAChR)。当从β2缺失突变小鼠制备突触体时，在任何脑区均未检测到尼古丁诱导的[H-3]多巴胺释放，这表明β2亚基是所有介导这种释放的nAChR所必需的。在每个脑区构建七种激动剂的剂量反应曲线。四个脑区突触体 [H-3] 多巴胺释放的药理学特性似乎相似。结果表明，所有四个区域都表达相同的 nAChR，尽管可能存在细微的区域差异。
The inhibition of uptake of [H-3]dopamine into synaptosomes prepared from four mouse brain regions was investigated. The inhibition curves demonstrated that in three regions, striatum, nucleus accumbens, and olfactory tubercle, [H-3]dopamine was taken up exclusively by dopaminergic terminals. In frontal cortex, however, only a portion of the uptake was into dopaminergic terminals, with a larger amount taken up by noradrenergic terminals, and another small portion by serotonergic terminals. Release studies in frontal cortex indicated that in this region only dopaminergic and noradrenergic terminals are capable of packaging [H-3]dopamine in a form allowing vesicle-mediated release; additionally, only the dopaminergic terminals have functional presynaptic nAChRs that, when stimulated by nicotinic agonists, evoke [H-3]dopamine release. Agonist-stimulated [H-3]dopamine release was characterized from synaptosomes prepared from four mouse brain regions. alpha-Conotoxin MII was a partial inhibitor of dopamine release in all of the brain regions, which suggests that a minimum of two nicotinic cholinergic receptors (nAChRs) are expressed in the nerve terminals of all four brain regions. No nicotine-induced [H-3]dopamine release was detected in any brain region when the synaptosomes were prepared from beta2 null mutant mice, which indicates that the beta2 subunit is required for all nAChRs mediating this release. Dose-response curves were constructed for seven agonists in each of the brain regions. The pharmacological properties of synaptosomal [H-3]dopamine release appear similar across the four brain regions. The results suggest that all four regions express the same nAChRs, although subtle regional differences may exist.