[3H]spiroxatrine labels a serotonin1A-like site in the rat hippocampus.
[3H]spiroxatrine labels a serotonin1A-like site in the rat hippocampus.
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[3H]spiroxatrine 标记大鼠海马中的 5-羟色胺 1A 样位点。
DOI：
10.1016/0024-3205(87)90723-5
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发表时间：
1987
期刊：
影响因子：
6.1
通讯作者：
Yamamura,HI
中科院分区：
文献类型：
--
作者：
Nelson,DL;Monroe,PJ;Lambert,G;Yamamura,HI
[~ 3 H]Spiroxatrine作为一种潜在的配体标记大鼠海马5-HT_（1A）位点。在不存在和存在不同浓度的三种单胺神经递质的情况下，[3 H]螺沙丁胺的结合分析显示，5-羟色胺（5-HT）具有高亲和力（[3 H]螺沙丁胺结合位点的IC 50 = 20.7 nM，与5-HT 1位点的标记一致），而多巴胺和去甲肾上腺素的亲和力非常低（IC 50 =57600 nM和>10− 4 M）。[3 H]spiroxatrine结合的饱和度研究揭示了一个单一的人口与Kd=2.21 nM的网站。使用5-HT 1阿立哌酮、8-羟基-2-（二正丙基氨基）四氢萘、伊沙匹龙和WB 4101以及丁酰苯化合物螺哌隆和氟哌啶醇进行进一步药理学表征，得到的结果与[3 H]螺唑嘌呤标记的5-HT 1 A位点一致。该配体产生稳定的、可再现的结合，具有良好的特异性与非特异性结合比率。[3 H]spiroxatrine的结合是敏感的GTP，这表明该配体可能作为一种激动剂。这一点得到了以下发现的支持：螺沙丁胺抑制大鼠海马中毛喉素刺激的腺苷酸环化酶活性（一种拟议的5-HT 1A受体模型）。由于[3 H]spiroxatrine在结构上不同于其他目前可用的5-HT 1Asite放射性配体，它应该提供新的信息，这种假定的肾上腺素能受体的属性。
[3H]Spiroxatrine was examined as a potential ligand for the labeling of 5-HT1Asites in the rat hippocampus. Analysis of the binding of [3H]spiroxatrine in the absence and presence of varying concentrations of three monoamine neurotransmitters revealed that serotonin (5-HT) had high affinity (IC50= 20.7 nM for the [3H]spiroxatrine binding sites, consistent with the labeling of 5-HT1sites, while dopamine and norepinephrine had very low affinity (IC50=57600 nM and >10−4M respectively). Saturation studies of the binding of [3H]spiroxatrine revealed a single population of sites with a Kd=2.21 nM. Further pharmacologic characterization with the 5-HT1Aligands 8-hydroxy-2-(di-n-propylamino) tetralin, ipsapirone, and WB4101 and the butyrophenone compounds spiperone and haloperidol gave results that were consistent with [3H]spiroxatrine labeling 5-HT1Asites. This ligand produced stable, reproducible binding with a good ratio of specific to nonspecific binding. The binding of [3H]spiroxatrine was sensitive to GTP, suggesting that this ligand may act as an agonist. This was supported by the finding that spiroxatrine inhibits forskolin-stimulated adenylate cyclase activity (a proposed 5-HT1Areceptor model) in the rat hippocampus. Since [3H]spiroxatrine is structurally distinct from other currently available radioligands for the 5-HT1Asite, it should provide new information about the properties of this putative serotonergic receptor.