Characterization of [3H]Hemicholinium‐3 Binding Sites in Human Brain Membranes: A Marker for Presynaptic Cholinergic Nerve Terminals
Characterization of [3H]Hemicholinium‐3 Binding Sites in Human Brain Membranes: A Marker for Presynaptic Cholinergic Nerve Terminals
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人脑膜中 [3H]Hemicholinium-3 结合位点的表征：突触前胆碱能神经末梢的标记
作者：
J. Pascual;Antonio M. González;Á. Pazos
摘要：我们在这里报告了[3 H]hemicholinium-3（一种高亲和力胆碱摄取过程的选择性抑制剂）与人脑膜的结合特性。在所述测定条件下，[3 H]半胆碱-3的结合表现出生理条件对pH、温度和NaCl浓度的依赖性。纹状体结合被证明是特异性的，一个单一的网站，饱和，和可逆的，与10 nM的表观KD和82 fmol/mg蛋白质的Bmax。[3 H]半胆碱-3特异性结合表现出药理学特征和离子依赖性，提示生理学相关相互作用，与高亲和力胆碱摄取报告的结果相当。此外，特异性[3 H]hemicholinium-3结合表现出不均匀的区域分布：纹状体基底核>脊髓中脑=小脑≥海马>新皮质=前丘脑>后丘脑白色物质。这种分布与哺乳动物大脑中酶促胆碱能突触前标记物和高亲和力胆碱摄取的报告活性密切对应。这些结果与先前使用该放射性配体在大鼠脑中发现的结果之间没有显著差异。我们的研究结果首次证明了[3 H]hemicholinium-3结合位点在人脑中的存在，并强烈支持这种放射性配体结合载体位点介导胆碱能神经元上的高亲和力胆碱摄取过程的提议。因此，[3 H]hemicholinium-3结合可在死后人脑中用作突触前胆碱能末梢的选择性和可量化标记物。
Abstract: We report here on the binding properties of [3H]hemicholinium‐3, a selective inhibitor of the high‐affinity choline uptake process, to human brain membranes. Under the assay conditions described, the binding of [3H]hemicholinium‐3 exhibited a dependency of physiological conditions on pH, temperature, and NaCl concentrations. Striatal binding proved to be specific, to a single site, saturable, and reversible, with an apparent KD of 10 nM and a Bmax of 82 fmol/mg of protein. [3H]Hemicholinium‐3 specific binding exhibited a pharmacological profile and an ionic dependency suggestive of physiologically relevant interactions and comparable with those reported for the high‐affinity choline uptake. Moreover, specific [3H]hemicholinium‐3 binding exhibited an uneven regional distribution: striatum ≫ nucleus basalis > spinal cord ≫ midbrain = cerebellum ≧ hippocampus > neocortex = anterior thalamus > posterior thalamus ⋙ white matter. This distribution closely corresponds to the reported activity of both enzymatic cholinergic presynaptic markers and high‐affinity choline uptake in mammalian brain. There are no significant differences between these results and those previously found in the rat brain using this radioligand. Our results demonstrate, for the first time, the presence of [3H]hemicholinium‐3 binding sites in human brain and strongly support the proposal that this radioligand binds to the carrier site mediating the high‐affinity choline uptake process on cholinergic neurons. Thus, [3H]hemicholinium‐3 binding may be used in postmortem human brain as a selective and quantifiable marker of the presynaptic cholinergic terminals.
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[3H]马吲哚结合与纹状体膜中神经元多巴胺摄取位点相关。
影响因子：
5
作者：
Javitch,JA;Blaustein,RO;Snyder,SH
通讯作者：
Snyder,SH
化学破坏大细胞基底核后，大鼠前大脑皮质中钠依赖性[3H]hemicholinium-3结合位点的密度降低。
影响因子：
5
作者：
Vickroy,TW;Fibiger,HC;Roeske,WR;Yamamura,HI
通讯作者：
Yamamura,HI
影响因子：
56.9
作者：
COYLE, JT;PRICE, DL;DELONG, MR
通讯作者：
DELONG, MR
大鼠脑中 [3H]hemicholinium-3 的钠依赖性高亲和力结合：突触前胆碱能位点的潜在选择性标记。
影响因子：
6.1
作者：
Vickroy,TW;Roeske,WR;Yamamura,HI
通讯作者：
Yamamura,HI
血清素转运蛋白-丙咪嗪“受体”。
DOI：
--
发表时间：
1983
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Talvenheimo,J;Fishkes,H;Nelson,PJ;Rudnick,G
通讯作者：
Rudnick,G