Ahrens Jörg, Demir Reyhan, Leuwer Martin, de la Roche Jeanne, Krampfl Klaus, Foadi Nilufar, Karst Matthias, Haeseler Gertrud
Clinic for Anaesthesia and Critical Care Medicine, OE 8050, Hannover, Germany.
Pharmacology. 2009;83(4):217-22. doi: 10.1159/000201556. Epub 2009 Feb 10.
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 micromol/l and alpha(1)beta = 18.1 +/- 6.2 micromol/l). Direct activation of glycine receptors was observed at higher concentrations above 100 micromol/l (EC(50) values: alpha(1) = 132.4 +/- 12.3 micromol/l and alpha(1)beta = 144.3 +/- 22.7 micromol/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.
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关键作用。成年脊髓中的抑制性突触后传递主要涉及甘氨酸。大麻二酚是大麻的一种非精神活性植物成分。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，我们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显示出正变构调节作用（EC(50)值：α(1)=12.3±3.8微摩尔/升和α(1)β=18.1±6.2微摩尔/升）。在高于100微摩尔/升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微摩尔/升和α(1)β=144.3±22.7微摩尔/升）。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点。
