Honokiol and magnolol selectively interact with GARAA receptor subtypes in vitro
Honokiol and magnolol selectively interact with GARAA receptor subtypes in vitro
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DOI：
10.1159/000056110
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发表时间：
2001-01-01
期刊：
影响因子：
3.1
通讯作者：
Nielsen, M
中科院分区：
文献类型：
--
作者：
Ai, JL;Wang, XM;Nielsen, M
和厚朴酚和厚朴酚已被鉴定为体外GABA（A）受体的调节剂。我们前期的研究表明和厚朴酚和厚朴酚对GABA（A）受体亚型可能具有选择性。在当前的研究中，通过H-3-蝇蕈醇和H-3-氟硝西泮对各种大鼠脑膜制备物和由Sf-9/杆状病毒系统表达的人重组GABA（A）受体亚单位组合的结合试验，检查了这种可能性。一般来说，和厚朴酚和厚朴酚对H-3-蝇蕈醇在非饱和结合试验中与各种膜制剂的结合具有类似的增强作用。和厚朴酚和厚朴酚优先增加H-3-蝇蕈醇结合海马相比，皮质和小脑（最大增强400%的控制）。对于亚基组合，和厚朴酚和厚朴酚对含有α（2）亚基的组合具有更强的增强作用（最大增强为对照的400-450%）。这种作用不依赖于γ亚基。在饱和结合试验中，厚朴酚影响结合位点的数量（约。4-在含有α（2）的组合上的折叠）或结合亲和力与此相反，和诺酮仅增加α（2）β（3）γ（2s）和α（2）β（3）组合上的结合位点，而α（1）、β（2）、γ（2S）和α（1）、β（2）结合位点的数目和亲和力均不同。这些结果表明和厚朴酚和厚朴酚对不同的GABA（A）受体亚型具有一定的选择性。与GABA（A）受体相互作用的性质及其选择性可能是这两种化合物体内效应的原因。版权所有（C）2001 S. Kerger AG，巴塞尔。
Honokiol and magnolol have been identified as modulators of the GABA(A) receptors in vitro. Our previous study suggested a possible selectivity of honokiol and magnolol on GABA(A) receptor subtypes. This possibility was examined in the current study by H-3-muscimol and H-3-flunitrazepam binding assays on various rat brain membrane preparations and human recombinant GABA(A) receptor subunit combinations expressed by the Sf-9/baculovirus system. Generally, honokiol and magnolol have a similar enhancing effect on H-3-muscimol binding to various membrane preparations in nonsaturation binding assays. Honokiol and magnolol preferentially increased H-3-muscimol binding to hippocampus compared to cortex and cerebellum (with a maximum enhancement of 400% of control). As for subunit combinations, honokiol and magnolol have a more potent enhancing effect on alpha (2) subunit containing combinations (with a maximum enhancement of 400-450% of control). This action was independent of the gamma subunit. In saturation binding assays, magnolol affected either the number of binding sites (ca. 4-fold on alpha (2) containing combinations) or the binding affinity (on alpha (1) containing combinations) of H-3-muscimol binding to various GABA(A) receptor subunit combinations, In contrast, honokiol increased only binding sites on alpha (2)beta (3)gamma (2s) and alpha (2)beta (3) combinations, but both the number of binding sites and the binding affinity on alpha (1)beta (2)gamma (2S) and alpha (1)beta (2) combinations, These results indicate that honokiol and magnolol have some selectivity on different GABA(A) receptor subtypes. The property of interacting with GABA(A) receptors and their selectivity could be responsible for the reported in vivo effects of these two compounds. Copyright (C) 2001 S. Kerger AG, Basel.