Diazepam-insensitive GABAA receptors in rat cerebellum and thalamus.
Diazepam-insensitive GABAA receptors in rat cerebellum and thalamus.
复制标题
大鼠小脑和丘脑中对地西泮不敏感的 GABAA 受体。
DOI：
10.1016/0014-2999(96)00349-4
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发表时间：
1996
影响因子：
5
通讯作者：
Olsen,RW
中科院分区：
文献类型：
--
作者：
Huh,KH;Endo,S;Olsen,RW
GABAA受体结合位点主要存在于小脑膜上：安定敏感的[~3H]Ro15-4513结合部位、不敏感的[~3H]Ro15-4513结合部位和高亲和力的[~3H]蝇草醇结合部位。免疫沉淀法显示，这三个群体都含有β亚基，抗体可识别所有β亚基。β3亚型的β亚基在所有三个群体中都存在，但每个群体中只有相似的低比例(<；20%)。因此，大多数含有β3以外的β亚基(β2和β1)，并且β3亚基不选择性地与三个结合群体中的任何一个相关或缺失。抗γ2亚基的抗体沉淀出类似的[~H]Ro15-4513、[~H]氟硝西潘和[~3H]蝇草酚结合部位，表明γ-2亚基存在于高亲和力的蝇毒酚结合亚型中，以及相当一部分地西安定不敏感的[~3H]Ro15-4513结合部位。在SDSPAGE上确定56 kDaα6亚基为[~3H]Ro15-4513结合小脑的安定不敏感部位的条件下，在大鼠丘脑中不能亲和标记与[~3H]Ro15-4513结合的多肽。这些结果表明，丘脑中的α4亚基主要参与与蝇草酚结合的亚基组合，但不参与任何苯二氮卓类位点配体的结合。
There major populations of GABAAreceptor binding sites are present in cerebellar membranes: diazepam-sensitive [3H]Ro15-4513 binding sites, diazepam-insensitive [3H]Ro15-4513 binding sites and high-affinity [3H]muscimol binding sites. All three populations contain a β subunit as shown by immunoprecipitation with antibodies that recognize all β subunits. The β3 subtype of β subunit is contained in all three populations, but only a similar low fraction (< 20%) in each. Thus, the majority contain β subunits other than β3 (β2 and β1) and β3 subunits are not selectively associated with nor lacking in any of the three binding populations. Antibodies to the γ2 subunit precipitated similar fractions of [3H]Ro15-4513, [3H]flunitrazepam and [3H]muscimol binding sites, showing that γ2 subunits are present in high-affinity muscimol binding isoforms, as well as a significant fraction of the diazepam-insensitive [3H]Ro15-4513 binding sites. Under conditions that identify the 56 kDa α6 subunit on SDS-PAGE as the diazepam-insensitive site of [3H]Ro15-4513 binding in cerebellum, no polypeptide showing diazepam-insensitive binding of [3H]Ro15-4513 could be photoaffinity-labeled in rat thalamus. These results suggest that α4 subunits in the thalamus participate primarily in subunit combinations which bind muscimol but not any benzodiazepine site ligands.