...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Biochemistry >Receptor desensitization by neurotransmitters in membranes: are neurotransmitters the endogenous anesthetics?
【24h】

Receptor desensitization by neurotransmitters in membranes: are neurotransmitters the endogenous anesthetics?

机译：膜中神经递质使受体脱敏：神经递质是内源性麻醉药吗？

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

A mechanism of anesthesia is proposed that addresses one of the most troubling peculiarities of general anesthesia: the remarkably small variability of sensitivity within the human population and across a broad range of animal phyla. It is hypothesized that in addition to the rapid, saturable binding of a neurotransmitter to its receptor that results in activation, the neurotransmitter also acts indirectly on the receptor by diffusing into the postsynaptic membrane and changing its physical properties, causing a shift in receptor conformational equilibrium (desensitization). Unlike binding, this slower indirect mechanism is nonspecific: each neurotransmitter will, in principle, affect all receptors in the membrane. For proteins modeled as having only resting and active conformational states, time-dependent ion currents are predicted that exhibit many characteristics of desensitization for both inhibitory and excitatory channels. If receptors have been engineered to regulate the time course of ion currents by this mechanism, then (a) mutations that significantly alter receptor sensitivity to this effect would be lethal and (b) by design, excitatory receptors would be inhibited, but inhibitory receptors activated, so that their effects are not counterproductive. The wide range of exogenous molecules that affect the physical properties of membranes as do neurotransmitters, but that do not bind to receptors, would thus inhibit excitatory channels and activate inhibitory channels, i.e., they would act as anesthesics. The endogenous anesthetics would thus be the neurotransmitters, the survival advantage conferred by their proper membrane-mediated desensitization of receptors explaining the selection pressure for anesthesic sensitivity.
机译：提出了一种麻醉机制，该机制解决了全身麻醉中最令人困扰的特性之一：在人群中以及在广泛的动物门区域内，敏感性的变异性非常小。据推测，除了神经递质与其受体的快速，饱和结合导致激活外，神经递质还通过扩散到突触后膜中并改变其物理性质，间接作用于受体，从而引起受体构象平衡的偏移。 （脱敏）。与结合不同，这种较慢的间接机制是非特异性的：原则上，每种神经递质都会影响膜中的所有受体。对于建模为仅具有静止和活跃构象状态的蛋白质，预测了随时间变化的离子电流对抑制性和兴奋性通道均表现出许多脱敏特性。如果通过这种机制设计了受体来调节离子电流的时程，则（a）显着改变受体对该效应的敏感性的突变将是致命的，并且（b）通过设计，兴奋性受体将被抑制，但抑制性受体被激活，因此其效果不会适得其反。像神经递质一样，影响膜的物理性质但不与受体结合的各种各样的外源分子将抑制兴奋性通道并激活抑制性通道，即它们将充当麻醉剂。因此，内源性麻醉药将是神经递质，它们的适当的膜介导的受体脱敏作用赋予了其生存优势，从而解释了麻醉敏感性的选择压力。

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