• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Critical role of calcitonin gene-related peptide receptors in cortical spreading depression
【24h】

Critical role of calcitonin gene-related peptide receptors in cortical spreading depression

机译：降钙素基因相关肽受体在皮质扩散抑制中的关键作用

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Cortical spreading depression (CSD) is a key pathogenetic step in migraine with aura. Dysfunctions of voltage-dependent and receptor-operated channels have been implicated in the generation of CSD and in the pathophysiology of migraine. Although a known correlation exists between migraine and release of the calcitonin gene-related peptide (CGRP), the possibility that CGRP is involved in CSD has not been examined in detail. We analyzed the pharmacological mechanisms underlying CSD and investigated the possibility that endogenous CGRP contributes to this phenomenon. CSD was analyzed in rat neocortical slices by imaging of the intrinsic optical signal. CSD was measured as the percentage of the maximal surface of a cortical slice covered by the propagation of intrinsic optical signal changes during an induction episode. Reproducible CSD episodes were induced through repetitive elevations of extracellular potassium concentration. AMPA glutamate receptor antagonism did not inhibit CSD, whereas NMDA receptor antagonism did inhibit CSD. Blockade of voltage-dependent sodium channels by TTX also reduced CSD. CSD was also decreased by the antiepileptic drug top-iramate, but not by carbamazepine. Interestingly, endogenous CGRP was released in the cortical tissue in a calcium-dependent manner during CSD, and three different CGRP receptor antagonists had a dose-dependent inhibitory effect on CSD, suggesting a critical role of CGRP in this phenomenon. Our findings show that both glutamate NMDA receptors and voltage-dependent sodium channels play roles in CSD. They also demonstrate that CGRP antagonism reduces CSD, supporting the possible use of drugs targeting central CGRP receptors as antimigraine agents.
机译：皮层扩散抑制（CSD）是先兆性偏头痛的关键致病步骤。电压依赖性和受体操纵的通道的功能障碍与CSD的产生和偏头痛的病理生理学有关。尽管偏头痛与降钙素基因相关肽（CGRP）的释放之间存在已知的相关性，但尚未详细研究CGRP参与CSD的可能性。我们分析了CSD的药理机制，并研究了内源性CGRP促成这一现象的可能性。通过对内在光信号成像，在大鼠新皮质切片中分析了CSD。 CSD测量为诱导发作期间内在光信号变化的传播所覆盖的皮质切片最大表面的百分比。可重复的CSD发作是通过细胞外钾浓度的反复升高诱导的。 AMPA谷氨酸受体拮抗作用不抑制CSD，而NMDA受体拮抗作用却抑制CSD。 TTX对电压依赖性钠通道的阻断也降低了CSD。抗癫痫药top-iramate还可降低CSD，但卡马西平则不能降低CSD。有趣的是，内源性CGRP在CSD期间以钙依赖的方式在皮质组织中释放，并且三种不同的CGRP受体拮抗剂对CSD具有剂量依赖的抑制作用，表明CGRP在此现象中起关键作用。我们的发现表明，谷氨酸NMDA受体和电压依赖性钠通道均在CSD中起作用。他们还证明了CGRP拮抗作用可降低CSD，支持可能将靶向中心CGRP受体的药物用作抗偏头痛药物。

著录项

  • 来源
  • 作者

    Alessandro Tozzi; Antonio de lure; Massimiliano Di Filippo; Cinzia Costa; Stefano Caproni; Antonio Pisani; Paola Bonsi; Barbara Picconi; Letizia M. Cupini; Serena Materazzi; Pierangelo Geppetti; Paola Sarchielli; and Paolo Calabresi;

  • 作者单位

    Clinica Neurologica, Universita di Perugia, 06156 Perugia, Italy,Laboratorio di Neurofisiologia, Fondazione Santa Lucia, Istituto di Ricovero e Cura a Carattere Scientifico, 00143 Rome, Italy;

    Clinica Neurologica, Universita di Perugia, 06156 Perugia, Italy;

    Clinica Neurologica, Universita di Perugia, 06156 Perugia, Italy;

    Clinica Neurologica, Universita di Perugia, 06156 Perugia, Italy;

    Clinica Neurologica, Universita di Perugia, 06156 Perugia, Italy;

    Laboratorio di Neurofisiologia, Fondazione Santa Lucia, Istituto di Ricovero e Cura a Carattere Scientifico, 00143 Rome, Italy;

    Laboratorio di Neurofisiologia, Fondazione Santa Lucia, Istituto di Ricovero e Cura a Carattere Scientifico, 00143 Rome, Italy;

    Laboratorio di Neurofisiologia, Fondazione Santa Lucia, Istituto di Ricovero e Cura a Carattere Scientifico, 00143 Rome, Italy;

    Reparto di Neurologia, Ospedale Sant'Eugenio, 00144 Rome, Italy;

    Dipartimento di Farmacologia Preclinica e Clinica and Centra Cefalee, Universita di Firenze, 50139 Florence, Italy;

    Dipartimento di Farmacologia Preclinica e Clinica and Centra Cefalee, Universita di Firenze, 50139 Florence, Italy;

    Clinica Neurologica, Universita di Perugia, 06156 Perugia, Italy;

    Clinica Neurologica, Universita di Perugia, 06156 Perugia, Italy,Laboratorio di Neurofisiologia, Fondazione Santa Lucia, Istituto di Ricovero e Cura a Carattere Scientifico, 00143 Rome, Italy;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

    cortex; epilepsy; headache; pain;

    机译：皮质癫痫;头痛;痛;

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号