Decreased high-affinity binding of [3H]muscimol to cerebral synaptic membranes of scrapie-infected mice.

Decreased high-affinity binding of [3H]muscimol to cerebral synaptic membranes of scrapie-infected mice.
复制标题

[3H]蝇蕈醇与痒病感染小鼠大脑突触膜的高亲和力结合减少。

DOI:
10.1111/j.1471-4159.1984.tb09733.x
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发表时间:
1984
影响因子:
4.7
通讯作者:
Somerville,RA
Somerville,RA
中科院分区:
医学2区
文献类型:
--
作者:
Quinn,MR;Somerville,RA

文献摘要

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瘙痒病是一种传染性疾病,会导致中枢神经系统的进行性退化和死亡。虽然对瘙痒病进行了组织病理学研究,但对神经递质的改变知之甚少。临床感染瘙痒病的小鼠全脑粗突触膜(CSM)上的特异性[~3H]蝇硫醇结合量显著减少(p<0.01),约为对照组的73%。在被检查的大脑区域中,只与大脑CSM结合的区域显著减少(p<0.0001)。饱和曲线的Scatchard分析表明,瘙痒病小鼠脑CSM的高亲和力部位(Kd=8±3 nM)被取消,而低亲和力部位不受影响。瘙痒病不影响[~3H]氟硝西潘与脑CSM的结合,而GABA对瘙痒病小鼠和对照组小鼠脑CSM的刺激作用相同。这些结果表明,C57BL/6J小鼠体内的抓痒剂139A通过与苯二氮卓类受体无关的高亲和力GABA结合部位表现出部分中枢神经系统病理。
Scrapie is a transmissible disease that results in progressive degeneration of the central nervous system and death. Although scrapie has been studied histopathologically, relatively little is known concerning neurotransmitter alterations. Specific [3H]muscimol binding to whole brain crude synaptic membranes (CSM) from mice clinically affected with scrapie was significantly (p < 0.01) reduced, to approximately 73% of that of the controls. Of the brain regions examined, binding to only cerebral CSM was significantly (p < 0.0001) decreased. Scatchard analyses of saturation curves revealed that the high‐affinity (KD= 8 ± 3 nM) site for muscimol was abolished in cerebral CSM from scrapie‐infected mice, while the low‐affinity site was unaffected. Binding of [3H]flunitrazepam to cerebral CSM was unaffected by scrapie and was stimulated by GABA to the same extent in both scrapie and control mice. These results suggest that scrapie agent 139A in C57BL/6J mice manifests a portion of its CNS pathology via a high‐affinity GABA binding site that is unassociated with the benzodiazepine receptor.