• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Pharmacology, Biochemistry and Behavior >Cannabinoid receptor agonists from Conus venoms alleviate pain-related behavior in rats
【24h】

Cannabinoid receptor agonists from Conus venoms alleviate pain-related behavior in rats

机译：来自Conus Venoms的大麻素受体激动剂可缓解大鼠疼痛相关的行为

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

Cannabinoid (CB) receptor agonists show robust antinociceptive effects in various pain models. However, most of the clinically potent CB1 receptor-active drugs derived from cannabis are considered concerning due to psychotomimetic side effects. Selective CB receptor ligands that do not induce CNS side effects are of clinical interest. The venoms of marine snail Conus are a natural source of various potent analgesic peptides, some of which are already FDA approved. In this study we evaluated the ability of several Conus venom extracts to interact with CB1 receptor. HEK293 cells expressing CB1 receptors were treated with venom extracts and CB1 receptor internalization was analyzed by immunofluorescence. Results showed C. textile (C. Tex) and C. miles (C. Mil) samples as the most potent. These were serially subfractionated by HPLC for subsequent analysis by internalization assays and for analgesic potency evaluated in the formalin test and after peripheral nerve injury. Intrathecal injection of C. Tex and C. Mil subfractions reduced flinching/licking behavior during the second phase of formalin test and attenuated thermal and mechanical allodynia in nerve injury model. Treatment with proteolytic enzymes reduced CB1 internalization of subfractions, indicating the peptidergic nature of CB1 active component. Further HPLC purification revealed two potent antinociceptive subfractions within C. Tex with CB1 and possible CB2 activity, with mild to no side effects in the CB tetrad assessment. CB conopeptides can be isolated from these active Conus venom-derived samples and further developed as novel analgesic agents for the treatment of chronic pain using cell based or gene therapy approaches.
机译：大麻素（CB）受体激动剂在各种疼痛模型中表现出强烈的抗伤害作用。然而，大多数从大麻中提取的临床有效CB1受体活性药物由于拟精神病副作用而受到关注。不引起CNS副作用的选择性CB受体配体具有临床意义。海洋蜗牛圆锥虫的毒液是各种强效镇痛肽的天然来源，其中一些已经获得FDA批准。在这项研究中，我们评估了几种芋螺毒液提取物与CB1受体相互作用的能力。用蛇毒提取物处理表达CB1受体的HEK293细胞，并通过免疫荧光分析CB1受体的内化。结果显示，C.纺织（C.Tex）和C.迈尔斯（C.Mil）样品的效力最强。通过HPLC对其进行连续亚组分，以便随后通过内化分析进行分析，并在福尔马林试验和周围神经损伤后评估其镇痛效力。鞘内注射C.Tex和C.Mil亚组分可减少福尔马林试验第二阶段的畏缩/舔行为，并减轻神经损伤模型中的热性和机械性痛觉超敏反应。蛋白水解酶处理降低了CB1亚组分的内化，表明CB1活性成分的肽能性质。进一步的高效液相色谱纯化显示，C.Tex中有两种有效的抗伤害亚组分，具有CB1和可能的CB2活性，在CB四分体评估中具有轻微或无副作用。CB锥肽可以从这些活性圆锥毒液衍生样品中分离出来，并进一步开发为新型镇痛剂，用于使用基于细胞或基因疗法的方法治疗慢性疼痛。

著录项

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