• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>CNS drug reviews >Cortagine: behavioral and autonomic function of the selective CRF receptor subtype 1 agonist.
【24h】

Cortagine: behavioral and autonomic function of the selective CRF receptor subtype 1 agonist.

机译：肾上腺皮质激素：选择性CRF受体亚型1激动剂的行为和自主功能。

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

Corticotropin-releasing factor (CRF) is a neuropeptide and mediating component of neuroendocrine, autonomic, and behavioral processes associated with the stress response. The two receptor subtypes identified in the mammalian brain, CRF receptor subtype 1 (CRF1) and CRF2, are suggested to differentially modulate these processes. Manipulation of these receptors with selective CRF compounds and transgenic models has revealed, in most studies, a clear potentiation of the stress response through central activation of CRF1. However, pharmacological activation of CRF restricted to CRF1 has been limited by the availability of selective peptidic compounds. Recently, a highly selective CRF1 agonist, cortagine, has been developed. It was synthesized from chimeric intermediate sequences of ovine CRF, sauvagine, and human/rat CRF into a highly soluble peptide with strong affinity for CRF1 (IC(50) < 5 nM) and a very low binding preference for CRF2 (IC(50) > 500 nM). Affinity for the CRF binding protein (IC(50) > 1,000 nM) can be abolished by the addition of a glutamate residue on position 21 of the cortagine peptide sequence. Cortagine has recently been tested in a variety of preclinical models of behavior including the elevated-plus-maze (EPM), forced swim test (FST), homecage, and rat exposure test (RET). Preliminary characterization in the EPM and FST suggested that this compound elicits anxiogenic and antidepressant-like effects, respectively. Additional testing in the homecage and RET, which targets various elements of behavior, directs to a more potent anxiogenic profile of cortagine. In this review, we discuss the behavioral findings and the tests used to measure these effects. Finally, we also discuss preliminary findings of autonomic activation obtained by central injection of cortagine that support CRF1 involvement in the modulation of heart rate and heart rate variability.
机译：促肾上腺皮质激素释放因子（CRF）是神经肽，是与压力反应相关的神经内分泌，自主神经和行为过程的中介成分。在哺乳动物脑中鉴定出的两种受体亚型，即CRF受体亚型1（CRF1）和CRF2，被认为可以差异地调节这些过程。在大多数研究中，通过选择性CRF化合物和转基因模型对这些受体的处理揭示了通过CRF1的中央激活可以明显增强应激反应。但是，受限于CRF1的CRF的药理活化受到选择性肽化合物可用性的限制。近来，已经开发出高度选择性的CRF1激动剂，可卡汀。它是由绵羊CRF，鼠尾草素和人/大鼠CRF的嵌合中间序列合成为对CRF1（IC（50）<5 nM）具有强亲和力且对CRF2的结合偏好非常低（IC（50） > 500 nM）。 CRF结合蛋白（IC（50）> 1,000 nM）的亲和力可以通过在可卡汀肽序列的21位上添加谷氨酸残基来消除。最近，已经在各种行为的临床前模型中对可卡汀进行了测试，包括高迷宫（EPM），强迫游泳测试（FST），笼养和大鼠暴露测试（RET）。 EPM和FST的初步表征表明，该化合物分别引起焦虑和抗抑郁样作用。针对笼罩行为和行为的各种因素，对笼子和RET进行了额外的测试，从而发现了更强的可卡汀焦虑感。在这篇综述中，我们讨论了行为调查结果以及用于衡量这些影响的测试。最后，我们还讨论了通过集中注射可卡汀而获得的自主神经激活的初步发现，该激活支持CRF1参与心率和心率变异性的调节。

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