Iatsenko N M, Tsintsadze T Sh, Lozova N O
Fiziol Zh (1994). 2007;53(3):31-7.
Most of the pharmacological actions of cannabinoids are mediated by CB1 receptors. There is also evidence that these compounds can produce effects that are not mediated by the activation of identified cannabinoid receptors. Our data demonstrate that cannabinoids may directly affect the functioning of inhibitory glycine receptor (GlyR) channels. Here, we report that cannabinoid receptors agonist WIN 55,212-2, in a CB1 receptor independent manner, cause a significant potentiation of the amplitudes of glycine-activated currents (I(Gly)) in acutely isolated hippocampal CA3 and CA1 pyramidal neurons. The maximal potentiation by this compound was observed at the lowest concentration of glycine; with increasing concentrations of glycine, the potentiation significantly decreased. Also WIN 55,212-2 significantly accelerated the desensitization of Gly-induced chloride current and significantly decreased the rise time. The effects of WIN 55,212-2 on I(Gly) were not attenuated in the presence of CB1 receptor antagonist AM251, suggesting that CB1 receptor activation are not involved in action of cannabinoid on GlyRs. Altogether these data allow us to suggest the existence of a CB1R independent action of cannabinoids directly on glycine-activated currents, representing a novel antinociceptive mechanism of this compounds.
大麻素的大多数药理作用是由CB1受体介导的。也有证据表明，这些化合物可以产生并非由已确定的大麻素受体激活所介导的效应。我们的数据表明，大麻素可能直接影响抑制性甘氨酸受体（GlyR）通道的功能。在此，我们报告大麻素受体激动剂WIN 55,212-2以一种不依赖CB1受体的方式，使急性分离的海马CA3和CA1锥体神经元中甘氨酸激活电流（I(Gly)）的幅度显著增强。该化合物在最低浓度的甘氨酸时观察到最大增强作用；随着甘氨酸浓度的增加，增强作用显著降低。WIN 55,212-2还显著加速了甘氨酸诱导的氯离子电流的脱敏，并显著缩短了上升时间。在存在CB1受体拮抗剂AM251的情况下，WIN 55,212-2对I(Gly)的作用并未减弱，这表明CB1受体激活不参与大麻素对甘氨酸受体的作用。总之，这些数据使我们认为大麻素存在一种不依赖CB1R的直接作用于甘氨酸激活电流的作用，这代表了该化合物一种新的抗伤害感受机制。
