氨基烷基吲哚与NG108-15细胞中非大麻素结合位点的结合。
Binding of aminoalkylindoles to noncannabinoid binding sites in NG108-15 cells.
作者信息
Stark S, Pacheco M A, Childers S R
机构信息
Neuroscience Program, Bowman Gray School of Medicine, Wake Forest University, Winston-Salem, North Carolina 27157, USA.
出版信息
Cell Mol Neurobiol. 1997 Oct;17(5):483-93. doi: 10.1023/a:1026306804802.
Abstract
- Aminoalkylindoles, typified by WIN 55212-2, bind to G protein-coupled cannabinoid receptors in brain. Although cannabinoids inhibit adenylyl cyclase in NG108-15 neuroblastoma x glioma hybrid cells, cannabinoid receptor binding in these cells has not been described previously. This study compares pharmacological characteristics of [3H]WIN 55212-2 binding sites in rat cerebellar membranes and in NG108-15 membranes. 2. Although the KD of specified [3H]WIN 55212-2 binding was similar in brain and NG108-15 membranes, the Bmax was 10 times lower in NG108-15 than in cerebellar membranes. In both brain and NG108-15 membranes, aminoalkylindole analogues were relatively potent in displacing [3H]WIN 55212-2 binding. However, IC50 values for more traditional cannabinoids were significantly higher in NG108-15 membranes than in brain, e.g., the Ki values for CP55,940 were 1.2 nM in brain and > 5000nM in NG108-15 membranes. Moreover, sodium and GTP-gamma-S decreased [3H]WIN 55212-2 binding in brain but not in NG108-15 membranes. 3. These data suggest that WIN 55212-2 does not label traditional cannabinoid receptors in NG108-15 cells and that these novel aminoalkylindole binding sites are not coupled to G proteins.
摘要
- 以WIN 55212-2为代表的氨基烷基吲哚可与脑中的G蛋白偶联大麻素受体结合。尽管大麻素可抑制NG108-15神经母细胞瘤x胶质瘤杂交细胞中的腺苷酸环化酶，但此前尚未描述过这些细胞中大麻素受体的结合情况。本研究比较了大鼠小脑膜和NG108-15膜中[3H]WIN 55212-2结合位点的药理学特性。2. 尽管特定[3H]WIN 55212-2结合的解离常数（KD）在脑和NG108-15膜中相似，但NG108-15中的最大结合容量（Bmax）比小脑膜中的低10倍。在脑和NG108-15膜中，氨基烷基吲哚类似物在取代[3H]WIN 55212-2结合方面相对有效。然而，更传统大麻素的半数抑制浓度（IC50）值在NG108-15膜中显著高于脑，例如，CP55,940的抑制常数（Ki）值在脑中为1.2 nM，在NG108-15膜中>5000 nM。此外，钠和鸟苷三磷酸γ-硫酯（GTP-γ-S）可降低脑中[3H]WIN 55212-2的结合，但不影响NG108-15膜中的结合。3. 这些数据表明，WIN 55212-2在NG108-15细胞中未标记传统大麻素受体，且这些新的氨基烷基吲哚结合位点未与G蛋白偶联。
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