Aminoalkylindole binding in rat cerebellum: selective displacement by natural and synthetic cannabinoids.
Aminoalkylindole binding in rat cerebellum: selective displacement by natural and synthetic cannabinoids.
复制标题
大鼠小脑中氨基烷基吲哚的结合：天然和合成大麻素的选择性置换。
DOI：
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发表时间：
1993
影响因子：
3.5
通讯作者：
D. Haycock
中科院分区：
文献类型：
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作者：
J. Kuster;J. Stevenson;S. Ward;T. D'ambra;D. Haycock
描述了 WIN 55212-2 的结合测定，WIN 55212-2 是一种在啮齿类动物中具有抗伤害活性的氨烷基吲哚 (AAI)。 [3H]WIN 55212-2 与大鼠小脑膜的结合 Kd 为 2 nM，最大结合量为 1.2 pmol/mg 蛋白质。该过滤测定中的特异性结合大于 90%，可饱和、可逆、立体特异性、pH 敏感且热不稳定。 Na+、K+、Li+ 和不可水解的 GTP 类似物会降低结合，而 Mg++ 和 Ca++ 会增加结合。整个中枢神经系统中特异性结合位点的密度各不相同，其中小脑、海马和纹状体中的特异性结合位点密度最高，而延髓/脑桥和脊髓中的特异性结合位点密度最低。其他 AAI 对 WIN 55212-2 结合位点的结合亲和力与其抑制离体小鼠输精管神经元刺激收缩的效力相关。在 60 多种代表公认神经递质系统的化合物中，只有大麻素能有效抑制结合。大麻素对 AAI 结合的影响与竞争性抑制一致，表明 AAI 活性可能全部或部分通过与大麻素受体的相互作用介导。 AAI 似乎代表了一类结构新颖的化合物，可用于研究大麻素受体。
A binding assay for WIN 55212-2, an aminoalkylindole (AAI) with antinociceptive activity in rodents, is described. [3H]WIN 55212-2 bound to rat cerebellar membranes with a Kd of 2 nM and a maximum binding of 1.2 pmol/mg of protein. Specific binding in this filtration assay was greater than 90%, saturable, reversible, stereospecific, pH sensitive and heat labile. Binding was decreased by Na+, K+, Li+ and nonhydrolyzable analogs of GTP and increased by Mg++ and Ca++. The density of specific binding sites varied throughout the central nervous system with the highest found in the cerebellum, hippocampus and striatum and the lowest in the medulla/pons and spinal cord. The binding affinities of other AAIs for the WIN 55212-2 binding site correlated with their potencies for inhibiting neuronally stimulated contractions in the isolated mouse vas deferens. Of more than 60 compounds representing recognized neurotransmitter systems, only cannabinoids effectively inhibited binding. The effect of cannabinoids on AAI binding was consistent with competitive inhibition and suggests that AAI activity may be mediated in whole or in part by interaction with cannabinoid receptors. AAIs appear to represent a structurally novel class of compounds with which to study cannabinoid receptors.