Evidence for altered post-receptor modulation of the serotonin 2a receptor in schizophrenia
Evidence for altered post-receptor modulation of the serotonin 2a receptor in schizophrenia
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DOI：
10.1016/j.schres.2008.06.011
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发表时间：
2008-09-01
影响因子：
4.5
通讯作者：
Scarr, Elizabeth
中科院分区：
文献类型：
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作者：
Dean, Brian;Crossland, Nicola;Scarr, Elizabeth
我们已经表明，皮质5-羟色胺（2A）受体减少使用组织切片，但没有清洗膜，从同一队列的主题。这些不一致的发现使我们确定是否可以使用来自相同组织块的样本获得相似的结果。我们的研究使用单点饱和度分析来估计来自Brodmann 9区的组织切片、粗匀浆、膜富集和细胞溶质富集组织样品中的[H-3]酮色林结合位点的总数。与对照组相比，精神分裂症受试者的组织切片（平均值+/- SD：38 +/- 16 vs. 56 +/- 16 fmol/mg埃特; p = 0.008）和粗组织匀浆（131 +/- 53 vs. 168 +/- 38 fmol/mg蛋白; p < 0.05）的[H-3]酮色林结合水平显著降低。相比之下，放射性配体与膜富集（155 +/- 95 vs. 145 +/- 48 fmol/mg蛋白，p = 0.72）或胞质富集（8.6 +/- 14 vs. 7.5 +/- 10 mol/mg蛋白; p = 0.85）组织组分的结合无显著差异。值得注意的是，将10（-5）M利培酮或氯丙嗪作为CNS中残留抗精神病药物的替代物加入到对照受试者的粗匀浆中并不改变[H-3]酮色林结合。因此，我们的数据与以下假设一致：精神分裂症中5-羟色胺（2A）受体的明显减少是由于调节配体与5-羟色胺（2A）受体结合的调节因子水平改变，并且分离膜和胞质溶胶消除了这种调节控制。(C)2008 Elsevier B. V.保留所有权利。
We have shown a decrease in cortical serotonin(2A) receptors using tissue sections, but not with washed membranes, from the same cohort of subjects. These discrepant findings led us to determine if we could obtain similar results using samples from the same tissue block. Our studies used single-point saturation analyses to estimate the total number of [H-3]ketanserin binding sites in tissue sections, crude homogenate, membrane-enriched and cytosol-enriched tissue samples from Brodmann's area 9. There were significant decreases in the levels of [H-3]ketanserin binding using tissue sections (mean +/- SD: 38 +/- 16 vs. 56 +/- 16 fmol/mg ETE; p = 0.008) and crude tissue homogenates (131 +/- 53 vs. 168 +/- 38 fmol/mg protein; p < 0.05) from subjects with schizophrenia compared to that in controls. By contrast, there was no significant difference in radioligand binding to the membrane-enriched (155 +/- 95 vs. 145 +/- 48 fmol/mg protein, p = 0.72) or cytosol-enriched (8.6 +/- 14 vs. 7.5 +/- 10 mol/mg protein; p = 0.85) tissue fraction. significantly, adding 10(-5) M risperidone or chlorpromazine, as surrogates for residual antipsychotic drugs in the CNS, to crude homogenate from control subjects did not alter [H-3]ketanserin binding. Our data therefore is consistent with the hypothesis that apparent decreases in serotonin(2A) receptors in schizophrenia are due to altered levels of a regulatory factor(s) that modulates the binding of ligands to the serotonin(2A) receptor and that separating the membrane and cytosol removes this regulatory control. (C) 2008 Elsevier B.V. All rights reserved.