...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Pharmacological reports: PR >Acute and repeated treatment with the 5-HT 7 receptor antagonist SB 269970 induces functional desensitization of 5-HT 7 receptors in rat hippocampus
【24h】

Acute and repeated treatment with the 5-HT 7 receptor antagonist SB 269970 induces functional desensitization of 5-HT 7 receptors in rat hippocampus

机译：用5-HT 7受体拮抗剂SB 269970进行的急性反复治疗可诱导大鼠海马中5-HT 7受体的功能性脱敏

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

Background: SB 269970, a 5-HT 7 receptor antagonist may produce a faster antidepressant-like effect in animal models, than do antidepressant drugs, e.g., imipramine. The present work was aimed at examining the effect of single and repeated (14 days) administration of SB 269970 on the 5-HT 7 receptor in the hippocampus. Methods: The reactivity of 5-HT 7 receptors was determined using 5-carboxamidotryptamine (5-CT), which increased the bursting frequency of spontaneous epileptiform activity in hippocampal slices. Additionally, the effects of SB 269970 administration on the affinity and density of 5-HT 7 receptors were investigated using [ 3H]-SB 269970 and the influence of SB 269970 and imipramine on mRNA expression levels of Gα s and Gα 12 mRNA were studied using RT-qPCR. Results: Acute and repeated treatment with SB 269970 led to attenuation of the excitatory effects of activation of 5-HT 7 receptors. Neither single nor repeated administration of SB 269970 changed the mean affinity of 5-HT 7 receptors for [ 3H]-SB 269970. Repeated, but not single, administration of SB 269970 decreased the maximum density of [ 3H]-SB 269970 binding sites. While administration of imipramine did not change the expression of mRNAs for Gα s and Gα 12 proteins after both single and repeated administration of SB 269970, a reduction in Gα s and Gα 12 mRNA expression levels was evident. Conclusions: These findings indicate that even single administration of SB269970 induces functional desensitization of the 5-HT 7receptor system, which precedes changes in the receptor density. This mechanism may be responsible for the rapid antidepressantlike effect of the 5-HT 7 antagonist in animal models.
机译：背景：5-HT 7受体拮抗剂SB 269970在动物模型中可能比抗抑郁药（如丙咪嗪）产生更快的抗抑郁样作用。本工作旨在检查单次和重复（14天）SB 269970对海马5-HT 7受体的影响。方法：使用5-羧酰胺基色胺（5-CT）测定5-HT 7受体的反应性，这会增加海马切片中自发性癫痫样活动的爆发频率。此外，使用[3H] -SB 269970研究了SB 269970对5-HT 7受体亲和力和密度的影响，并使用SB 269970和丙咪嗪对Gαs和Gα12 mRNA的mRNA表达水平的影响进行了研究。实时定量PCR结果：SB 269970的急性和反复治疗导致5-HT 7受体激活的兴奋作用减弱。一次或重复施用SB 269970都不会改变5-HT 7受体对[3H] -SB 269970的平均亲和力。重复但不是一次施用SB 269970会降低[3H] -SB 269970结合位点的最大密度。在单次和重复施用SB 269970后，丙咪嗪的施用不会改变Gαs和Gα12蛋白的mRNA表达，但Gαs和Gα12 mRNA表达水平明显降低。结论：这些发现表明，即使单次施用SB269970也会引起5-HT 7受体系统的功能脱敏，这是在受体密度发生变化之前。这种机制可能是在动物模型中5-HT 7拮抗剂的快速抗抑郁样作用的原因。

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