SIGMA-1 AND SIGMA-2 SITES IN RAT-BRAIN - COMPARISON OF REGIONAL, ONTOGENIC, AND SUBCELLULAR PATTERNS
SIGMA-1 AND SIGMA-2 SITES IN RAT-BRAIN - COMPARISON OF REGIONAL, ONTOGENIC, AND SUBCELLULAR PATTERNS
复制标题
DOI：
10.1002/syn.890170307
复制
发表时间：
1994-07-01
期刊：
影响因子：
2.3
通讯作者：
SU, TP
中科院分区：
文献类型：
--
作者：
MCCANN, DJ;WEISSMAN, AD;SU, TP
建立了选择性标记大鼠脑膜匀浆中sigma-1和sigma-2位点的放射配体结合实验条件。采用5nm (+)[H-3] skf - 10047在300 nM二唑西平（MK-801）存在下进行选择性sigma-1测定。在1 μ M (+) skf - 10047存在下，使用5 nM [H-3]DTG进行选择性sigma-2测定。sigma-1和sigma-2结合在大脑区域的分布是不同的。虽然脑干产生最高水平的sigma-1结合，但它产生最低水平的sigma-2结合。海马体膜的情况正好相反。不同的个体发生模式也被观察到。在大脑发育过程中，Sigma-2结合显著减少，而sigma-1结合没有显著变化。在大鼠脑匀浆的亚细胞组分之间的分布模式是相似的。sigma-1和sigma-2位点在微粒体部分最富集，在突触体和线粒体部分都不富集。目前的结果表明，sigma-1和sigma-2位点是不同的实体；它们似乎不位于一个共同的大分子上，它们也不代表单一类型结合位点的两种不同的亲和力状态。虽然sigma-1和sigma-2位点的精确亚细胞位置仍有待确定，但我们得出的结论是，将这两种结合位点定位于质膜突触区域或线粒体的可能性很小。(C) 1994 Wiley-Liss, Inc。
Radioligand binding assay conditions were established for the selective labeling of sigma-1 and sigma-2 sites in membrane homogenates of rat brain. Selective sigma-1 assays were conducted using 5 nM (+)[H-3]SKF-10,047 in the presence of 300 nM dizocilpine (MK-801). Selective sigma-2 assays were conducted using 5 nM [H-3]DTG in the presence of 1 mu M (+)SKF-10,047. Distributions of sigma-1 and sigma-2 binding among brain regions were found to differ. While the brain stem yields the highest level of sigma-1 binding, it yields among the lowest levels of sigma-2 binding. The reverse is true in hippocampal membranes. Different ontogenetic patterns were also observed. Sigma-2 binding decreases substantially during brain development, whereas sigma-1 binding does not vary significantly. Patterns of distribution among subcellular fractions of rat brain homogenates were found to be similar. Both sigma-1 and sigma-2 sites are most enriched in microsomal fractions, and neither is enriched in synaptosomal or mitochondrial fractions. The present results suggest that sigma-1 and sigma-2 sites are distinct entities; they do not appear to be located on a common macromolecule, and they do not represent two different affinity states of a single type of binding site. While the precise subcellular locations of sigma-1 and sigma-2 sites remain to be determined, we conclude that localization of either type of binding site to synaptic regions of plasma membrane or to mitochondria is highly unlikely. (C) 1994 Wiley-Liss, Inc.