Seizure susceptibility alteration through 5-HT3 receptor: Modulation by nitric oxide
Seizure susceptibility alteration through 5-HT3 receptor: Modulation by nitric oxide
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DOI：
10.1016/j.seizure.2009.10.006
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发表时间：
2010-01-01
影响因子：
3
通讯作者：
Dehpour, Ahmad Reza
中科院分区：
文献类型：
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作者：
Gholipour, Taha;Ghasemi, Mehdi;Dehpour, Ahmad Reza
有一些证据表明，癫痫发作可以通过5-羟色胺（5-HT）衰减诱导或增加，而脑内5-羟色胺功能的增强（例如通过SSRI）已被报道为抗惊厥药。本研究旨在观察选择性5-HT 3通道/受体拮抗剂格拉司琼和激动剂SR 57227盐酸盐对戊四唑（PTZ）诱导的小鼠癫痫发作阈值的影响。用一氧化氮（NO）合酶抑制剂N-G-硝基-L-精氨酸甲酯（L-NAME）和NO前体L-精氨酸研究了这种效应与氮能系统的可能相互作用。SR57227（10 mg/kg，i.p.）高剂量格拉司琼（10 mg/kg，i. p.）被证明是诱发惊厥的将亚有效剂量的5-HT 3激动剂与L-NAME（5和60 mg/kg，i. p.，分别）发挥了显著的抗惊厥作用，而观察到亚有效剂量的格拉司琼（3 mg/kg）在加入L-精氨酸（75 mg/kg，i. p.）的情况下具有促惊厥作用。我们的数据表明，增强5-HT 3受体功能的结果在PTZ诱导的癫痫发作模型的抗惊厥作用，并在5-HT 3受体的选择性拮抗产生促惊厥作用。此外，NO系统可能在5-HT 3受体功能中起作用。(C)2009年英国癫痫协会。由爱思唯尔有限公司出版。保留所有钻机。
There is some evidence that epileptic seizures could be induced or increased by 5-hydroxytryptamine (5-HT) attenuation, while augmentation of serotonin functions within the brain (e.g. by SSRIs) has been reported to be anticonvulsant. This study was performed to determine the effect of selective 5-HT3 channel/receptor antagonist granisetron and agonist SR57227 hydrochloride on the pentylenetetrazole (PTZ)-induced seizure threshold in mice. The possible interaction of this effect with nitrergic system was also examined using the nitric oxide (NO) synthase inhibitor N-G-nitro-L-arginine methyl ester (L-NAME) and the NO precursor L-arginine. SR57227 (10 mg/kg, i.p.) significantly increased the seizure threshold compared to control group, while high dose granisetron (10 mg/kg, i.p.) proved proconvulsant. Co-administration of sub-effective doses of the 5-HT3 agonist With L-NAME (5 and 60 mg/kg, i.p., respectively) exerted a significant anticonvulsive effect, while sub-effective doses of granisetron (3 mg/kg) was observed to have a proconvulsive action with the addition of L-arginine (75 mg/kg, i.p.). Our data demonstrate that enhancement of 5-HT3 receptor function results in as anticonvulsant effect in the PTZ-induced seizure model, and that selective antagonism at the 5-HT3 receptor yields proconvulsive effects. Furthermore, the NO system may play a role in 5-HT3 receptor function. (C) 2009 British Epilepsy Association. Published by Elsevier Ltd. All rig s reserved.