在孤立的老鼠心脏中,阿片类和上腺素受体信号之间的"交叉通话"
1Laboratory of Cardiovascular Science, Gerontology Research Center, National Institute on Aging, Baltimore, Md 21224, USA.
Circulation
|April 15, 1997
概括
阿片类受体 (OPR) 与心脏中的β-上腺素受体 (β-AR) 相互作用. 德尔塔-OPR刺激通过降低cAMP来抑制β1-AR效应,这种效应由一个对PTX敏感的G (i/o) 蛋白介导.
科学领域:
- 心血管生理学心血管生理学
- 分子药理学分子药理学
- 神经心脏病学 神经心脏病学
背景情况:
- 心脏细胞具有甲基胺和阿片类受体 (OPR).
- 片类酸与心脏神经终端中的甲基荷兰胺一起释放.
- 研究OPR对β-上腺素受体 (β-AR) 刺激效应的影响至关重要.
研究的目的:
- 为了确定OPR刺激是否会影响隔离的老鼠心中的β-AR刺激.
- 阐明相互作用的机制,重点关注β-AR亚型和cAMP调节.
- 探索G (i/o) 蛋白在这种交叉谈话中的作用.
主要方法:
- 隔离的,同体积的老鼠心脏模型.
- 用诺拉皮内林 (NE),氨酸-恩基法林 (LE,三角形-OPR激动剂) 和福斯科林进行刺激.
- 测量左心室缩压 (LVSP) 和cAMP水平.
- 在机理学研究中使用OPR对手纳洛和百日咳毒素 (PTX).
- 对β2-AR激动剂 (Zinterol) 作用的评估.
主要成果:
- 上腺素 (NE) 增加了LVSP和cAMP.
- 氨酸-基法林 (LE) 抑制了NE诱导的LVSP和cAMP的增加.
- 勒的效应被纳洛逆转,表明了OPR的参与.
- LE没有影响由β2-AR激动剂调解的cAMP独立的内反应.
- 咳毒素 (PTX) 的预处理取消了LE的抑制作用,涉及G (i/o) 蛋白.
结论:
- 在delta-OPR和β1-AR信号通路之间存在强大的抑制交叉对话.
- 这种相互作用是由一个对PTX敏感的G蛋白介导的.
- 该机制涉及抑制腺环酶,降低大鼠心脏中的cAMP水平.
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