[3H]1-[2-(4-aminophenyl)ethyl]-4-(3-trifluoromethylphenyl)piperazine: a selective radioligand for 5-HT1A receptors in rat brain.
[3H]1-[2-(4-aminophenyl)ethyl]-4-(3-trifluoromethylphenyl)piperazine: a selective radioligand for 5-HT1A receptors in rat brain.
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[3H]1-[2-(4-氨基苯基)乙基]-4-(3-三氟甲基苯基)哌嗪：大鼠脑中5-HT1A受体的选择性放射性配体。
DOI：
10.1111/j.1471-4159.1986.tb12926.x
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发表时间：
1986
影响因子：
4.7
通讯作者：
Shih,JC
中科院分区：
文献类型：
--
作者：
Ransom,RW;Asarch,KB;Shih,JC
1-[2-（4-Aminophenyl）ethyl]-4-（3-trifluoromethylphenyl）piperazine（PAPP）抑制[3 H]5-羟色胺（5-HT，serotonin）与大鼠脑内5-HT 1A和5-HT 1B位点的结合，表观平衡解离常数（KD）分别为2.9和328 nM。合成了[3 H]PAPP，检查了其与中枢5-羟色胺受体的结合，并评价了其作为5-HT 1A受体放射性配体的潜在用途。含10 μ M 5-HT或1 μ M 8-羟基-2-（二正丙基氨基）四氢化萘来定义非特异性结合，[3 H]PAPP结合到大鼠皮质膜中的单一类别位点，aKD为1.6 nM，最大结合密度（Bmax）为162 fmol/mg蛋白质。d-麦角酸二乙基酰胺和5-HT，两种[3 H]5-HT结合的非选择性抑制剂，取代1 nM[3 H]PAPP，其效力与其对5-HT 1受体的亲和力相匹配。螺哌隆和8-羟基-2-（二正丙基氨基）四氢萘（区分[3 H]5-HT与5-HT 1A和5-HT 1B位点结合的两种化合物）根据其对5-HT 1A受体亚型的更高亲和力抑制[3 H]PAPP结合。此外，N-（间三氟甲基苯基）哌嗪和酮色林抑制[3 H]PAPP结合的能力反映了它们对5-HT 1A受体的低亲和力。还发现几种非β-胡萝卜素能化合物是[3 H]PAPP结合的相对较差的置换剂。5-羟色胺敏感性[3 H]PAPP位点的区域分布与大鼠皮质、海马、纹状体和小脑中5-HT 1A受体的密度相关。这些结果表明，[3 H]PAPP选择性地与大鼠脑内的5-HT 1A受体位点结合，并具有高亲和力。
1‐[2‐(4‐Aminophenyl)ethyl]‐4‐(3‐trifluoromethylphenyl)piperazine (PAPP) inhibits [3H]5‐hydroxytryptamine (5‐HT, serotonin) binding to 5‐HT1Aand 5‐HT1Bsites in rat brain with apparent equilibrium dissociation constants (KD) of 2.9 and 328 nM, respectively. [3H]PAPP was synthesized, its binding to central serotonin receptors was examined, and its potential usefulness as a 5‐HT1Areceptor radioligand was evaluated. With either 10 μM5‐HT or 1 μM8‐hydroxy‐2‐(di‐n‐propylamino)tetralin to define nonspecific binding, [3H]PAPP bound to a single class of sites in rat cortical membranes with aKDof 1.6 nMand a maximal binding density (Bmax) of 162 fmol/mg of protein.d‐Lysergic acid diethylamide and 5‐HT, two nonselective inhibitors of [3H]5‐HT binding, displaced 1 nM[3H]PAPP with a potency that matched their affinity for 5‐HT1receptors. Spiperone and 8‐hydroxy‐2‐(di‐n‐propylamino)tetralin, two compounds that discriminate [3H]5‐HT binding to 5‐HT1Aand 5‐HT1Bsites, inhibited [3H]PAPP binding in accordance with their much higher affinities for the 5‐HT1Areceptor subtype. Furthermore, the ability ofN‐(m‐trifluoromethylphenyl)piperazine and ketanserin to inhibit [3H]PAPP binding reflected their low affinities for the 5‐HT1Areceptor. Several nonserotonergic compounds were also found to be relatively poor displacers of [3H]PAPP binding. The regional distribution of serotonin‐sensitive [3H]PAPP sites correlated with the densities of 5‐HT1Areceptors in the cortex, hippocampus, corpus striatum, and cerebellum of the rat. These results indicate that [3H]PAPP binds selectively and with high affinity to 5‐HT1Areceptor sites in rat brain.