...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>British Journal of Pharmacology >Selection of distinct conformational states of the 5-HT_3 receptor by full and partial agonists
【24h】

Selection of distinct conformational states of the 5-HT_3 receptor by full and partial agonists

机译：通过完全和部分激动剂选择5-HT_3受体不同的构象状态

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

1 5-Hydroxytryptamine 5-HT_3 receptor-mediated ion currents evoked by 5-HT, quaternary 5-HT (5-HTQ), meta-chlorophenylbiguanide (mCPBG), dopamine and tryptamine in N1E-115 mouse neuroblastoma cells have been investigated in whole-cell voltage clamp and single channel patch clamp experiments. 2 The concentration-dependent activation and desensitization of the ion currents evoked by the agonists yield the potency order: mCPBG > 5-HTQ ≈ 5-HT > > tryptamine > dopamine, and the efficacy order: 5-HT ≈ mCPBG ≈ 5-HTQ > > dopamine ≈ tryptamine. Thus, 5-HT, 5-HTQ and mCPBG are full agonists, whereas dopamine and tryptamine are partial agonists at the 5-HT_3 receptor. 3 Full and partial agonists cause complete cross-desensitization and activate single channels with similar conductances and open lifetimes. This shows that full and partial agonists act on the same population of 5-HT_3 receptors. 4 The time course of recovery from desensitization depends on the agonist used. Recovery from partial agonist-induced desensitization is single exponential, whereas the desensitization induced by full agonists recovers with sigmoid kinetics, suggesting at least 3 steps between 4 states. 5 During the process of recovery from cross-desensitization, the full agonists activate a larger fraction of the 5-HT_3 receptors than the partial agonists, irrespective of the agonist used to induce desensitization. 6 It is concluded that full and partial agonists induce distinct desensitized states and, during recovery from desensitization, recognize distinct conformations of unoccupied 5-HT_3 receptors. This conformational selection is likely to account for the different efficacies of full and partial 5-HT_3, receptor agonists.
机译：完整研究了N1E-115小鼠神经母细胞瘤细胞中由5-HT，季5-HT（5-HTQ），间氯苯基双胍（mCPBG），多巴胺和色胺引起的1 5-羟色胺5-HT_3受体介导的离子电流。电池电压钳和单通道膜片钳实验。 2激动剂引起的离子电流的浓度依赖性激活和脱敏产生效价顺序：mCPBG> 5-HTQ≈5-HT色胺>多巴胺，功效顺序：5-HT≈mCPBG≈5-HTQ 多巴胺≈色胺。因此，5-HT，5-HTQ和mCPBG是完全激动剂，而多巴胺和色胺是5-HT_3受体的部分激动剂。 3完全和部分激动剂会导致完全交叉脱敏，并以相似的电导和开放寿命激活单个通道。这表明完全和部分激动剂作用于相同的5-HT_3受体群体。 4脱敏恢复的时间过程取决于所用的激动剂。从部分激动剂引起的脱敏作用的恢复是单指数的，而完全激动剂引起的脱敏作用以乙状结肠动力学恢复，表明在4种状态之间至少有3个步骤。 5在从交叉脱敏反应中恢复的过程中，与用于引起脱敏作用的激动剂相比，完全激动剂比部分激动剂能激活更大比例的5-HT_3受体。 6结论是，完全激动剂和部分激动剂会诱导出不同的脱敏状态，并且在从脱敏状态恢复期间，会识别出未被占用的5-HT_3受体的不同构象。这种构象选择可能解释了全部和部分5-HT_3受体激动剂的不同功效。

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