The Nonpsychotropic Cannabinoid Cannabidiol Modulates and Directly Activates Alpha-1 and Alpha-1-Beta Glycine Receptor Function
The Nonpsychotropic Cannabinoid Cannabidiol Modulates and Directly Activates Alpha-1 and Alpha-1-Beta Glycine Receptor Function
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DOI：
10.1159/000201556
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发表时间：
2009-01-01
期刊：
影响因子：
3.1
通讯作者：
Haeseler, Gertrud
中科院分区：
文献类型：
--
作者：
Ahrens, Joerg;Demir, Reyhan;Haeseler, Gertrud
脊髓背角内抑制性突触传递的丧失在炎症或神经损伤后慢性疼痛的发展中起着关键作用。成人脊髓中的抑制性突触后传递主要涉及甘氨酸。大麻二酚是大麻的非精神植物成分。由于我们假设大麻二酚的非 CB 受体机制可能有助于其抗炎和神经保护作用，因此我们通过使用全细胞膜片钳技术研究了大麻二酚与士的宁敏感的 α(1) 和 α(1)β 甘氨酸受体的相互作用。大麻二酚在低微摩尔浓度范围内表现出积极的变构调节作用（EC（50）值：α（1）= 12.3 +/- 3.8 μ mol/l和α（1）β = 18.1 +/- 6.2 μ mol/l）。在高于 100 μmol/l 的较高浓度下观察到甘氨酸受体的直接激活（EC(50) 值：α(1) = 132.4 +/- 12.3 μmol/l 和 α(1)beta = 144.3 +/- 22.7 μmol/l）。这些体外结果表明士的宁敏感的甘氨酸受体可能是大麻二酚介导其一些抗炎和神经保护特性的靶标。版权所有 (C) 2009 S. Karger AG，巴塞尔
Loss of inhibitory synaptic transmission within the dorsal horn of the spinal cord plays a key role in the development of chronic pain following inflammation or nerve injury. Inhibitory postsynaptic transmission in the adult spinal cord involves mainly glycine. Cannabidiol is a nonpsychotropic plant constituent of Cannabis sativa. As we hypothesized that non-CB receptor mechanisms of cannabidiol might contribute to its anti-inflammatory and neuroprotective effects, we investigated the interaction of cannabidiol with strychnine-sensitive alpha(1) and alpha(1)beta glycine receptors by using the whole-cell patch clamp technique. Cannabidiol showed a positive allosteric modulating effect in a low micromolar concentration range (EC(50) values: alpha(1) = 12.3 +/- 3.8 mu mol/l and alpha(1)beta = 18.1 +/- 6.2 mu mol/l). Direct activation of glycine receptors was observed at higher concentrations above 100 mu mol/l (EC(50) values: alpha(1) = 132.4 +/- 12.3 mu mol/l and alpha(1)beta = 144.3 +/- 22.7 mu mol/l). These in vitro results suggest that strychnine-sensitive glycine receptors may be a target for cannabidiol mediating some of its anti-inflammatory and neuroprotective properties. Copyright (C) 2009 S. Karger AG, Basel