Vanilloid VR1 receptor is involved in rimonabant-induced neuroprotection
Vanilloid VR1 receptor is involved in rimonabant-induced neuroprotection
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DOI：
10.1038/sj.bjp.0706656
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发表时间：
2006-03-01
影响因子：
7.3
通讯作者：
Sala, M
中科院分区：
文献类型：
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作者：
Pegorini, S;Zani, A;Sala, M
1最近，已经提出了利莫那班的潜在神经保护作用，独立于CB 1受体相互作用。在本研究中，瞬时受体电位通道香草酸亚家族成员1，命名为VR 1，在利莫那班对沙土鼠全脑缺血的神经保护作用中的作用进行了研究。再循环后5分钟，剂量依赖性地拮抗缺血诱导的脑电图（EEG）总频谱功率的降低，并在缺血后7天恢复相对频带分布。3（0.125 - 0.5 mg kg（-1））完全防止缺血后1天缺血诱导的过度运动和被动回避任务中评估的记忆障碍，缺血后第7天，给予利莫那班0.25和0.5 mg kg（-1）的动物中CA（1）分区锥体细胞的存活率分别为91%和96%，与载体组相比。较高剂量无保护作用。5利莫那班诱导的保护作用呈钟形曲线，最大活性剂量为0.25和0.5 mg/kg（-1至1.6 mg/kg辣椒平（0.01 mg kg（-1）），一种选择性VR 1香草酸受体拮抗剂，完全逆转了利莫那班诱导的对EEG平坦化的神经保护作用，7这些发现表明，VR 1香草酸受体参与利莫那班的神经保护作用，即使其他机制可能有助于这种作用。
1 Recently, a potential neuroprotective effect of rimonabant, independent of the CB1 receptor interaction, has been proposed. In the present study, the role of transient receptor potential channel vanilloid subfamily member 1, named VR1, on neuroprotective effect of rimonabant, on global cerebral ischemia in gerbils, was investigated.2 Rimonabant (0.05 - 3 mg kg(-1)), given i. p. 5 min after recirculation, dose dependently antagonized the ischemia-induced decrease in electroencephalographic ( EEG) total spectral power and restored relative frequency band distribution 7 days after ischemia.3 Rimonabant (0.125 - 0.5 mg kg(-1)) fully prevented ischemia-induced hyperlocomotion 1 day after ischemia and memory impairment evaluated in a passive avoidance task, 3 days after ischemia.4 At 7 days after ischemia, the survival of pyramidal cells, in the CA(1) subfield, was respectively 91 and 96%, in the animals given rimonabant 0.25 and 0.5 mg kg(-1), compared to the vehicle group. Higher doses were not protective.5 The protection induced by rimonabant followed a bell-shaped curve, the maximal active doses being 0.25 and 0.5 mg kg(-1).6 Capsazepine (0.01 mg kg(-1)), a selective VR1 vanilloid receptor antagonist, completely reversed rimonabant-induced neuroprotective effects against EEG flattening, memory impairment and CA1 hippocampal neuronal loss.7 These findings suggest that VR1 vanilloid receptors are involved in rimonabant's neuroprotection even if other mechanisms can contribute to this effect.