Involvement of transient receptor potential vanilloid type 1 channels in the pro-convulsant effect of anandamide in pentylenetetrazole-induced seizures
Involvement of transient receptor potential vanilloid type 1 channels in the pro-convulsant effect of anandamide in pentylenetetrazole-induced seizures
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DOI：
10.1016/j.eplepsyres.2012.02.003
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发表时间：
2012-06-01
影响因子：
2.2
通讯作者：
Umathe, Sudhir N.
中科院分区：
文献类型：
--
作者：
Manna, Shyamshree S. S.;Umathe, Sudhir N.
大麻素，CB 1受体的内源性激动剂，也激活TRPV 1，但在更高的浓度。研究表明，大麻素通过CB 1受体具有抗惊厥活性，而其通过TRPV 1的作用仍然不明确。因此，本研究探讨了花生四烯酸对戊四唑诱导的癫痫发作的影响与TRPV 1或CB 1受体拮抗剂预处理的小鼠。急性脑室内给药低剂量的大麻素（10，20，或40微克/小鼠）产生抗惊厥作用，而促惊厥作用在高剂量（80或100微克/小鼠）是明显的。有趣的是，AM 251（2 μ g/小鼠），一种CB 1拮抗剂预处理阻断了抗惊厥作用，但增强了促惊厥作用。相反，在存在无活性剂量的辣椒平（1 μ g/小鼠），TRPV 1拮抗剂，anandamide表现出显着的抗惊厥作用，即使在高剂量，其抗惊厥作用没有变化。此外，用辣椒素，TRPV 1激动剂（10或100 μ g/小鼠）处理的小鼠表现出促惊厥活性，该活性被辣椒平预处理阻断。然而，辣椒平本身在10或100 μ g/小鼠剂量下表现出抗惊厥作用。与大麻素一样，增加其突触浓度的药物（AM404和URB 597）产生了类似的双相效应。因此，这些结果表明，花生四烯酸酰胺通过分别激活TRPV 1和CB 1受体而表现出促惊厥和抗惊厥活性。(C)2012 Elsevier B. V.保留所有权利。
Anandamide, an endogenous agonist of CB1 receptors, also activates TRPV1 but at a higher concentration. Studies demonstrate the anticonvulsant activity of anandamide via CB1 receptors, while its action through TRPV1 is still ambiguous. Thus, the present study investigated the influence of anandamide on pentylenetetrazole-induced seizures in mice pretreated with TRPV1 or CB1 receptor antagonists. Acute intracerebroventricular administration of low doses of anandamide (10, 20, or 40 mu g/mouse) produced anticonvulsant effect, while the pro-convulsant effect was evident at high doses (80 or 100 mu g/mouse). Interestingly, AM251 (2 mu g/mouse), a CB1, antagonist pretreatment blocked the anticonvulsant effect, but augmented the pro-convulsant effect. Conversely, in the presence of inactive dose of capsazepine (1 mu g/mouse), a TRPV1 antagonist, anandamide exhibited significant anticonvulsant effect even at high doses with no change in its anticonvulsant effect. Moreover, mice treated with capsaicin, a TRPV1 agonist (10, or 100 mu g/mouse) exhibited pro-convulsant activity that was blocked by capsazepine pretreatment. However, capsazepine, per se at doses 10 or 100 mu g/mouse exhibited anticonvulsant effect. Like anandamide, the agents (AM404 and URB597), which increase its synaptic concentrations produced similar biphasic effects. Thus, these results indicate that anandamide exhibits both pro- and anticonvulsant activities by activating TRPV1 and CB1 receptor respectively. (C) 2012 Elsevier B.V. All rights reserved.