CONTRASTING CELLULAR EFFECTS OF BETA1 AND BETA2 ADRENERGIC RECEPTOR STIMULATION

对比 β1 和 β2 肾上腺素能受体刺激的细胞效应

• 批准号: 3802249
• 负责人: R P XIAO
• 金额: --
• 依托单位: NATIONAL INSTITUTE ON AGING
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3802249
• 关键词: beta adrenergic receptor; beta antiadrenergic agent; calcium flux; cyclic AMP; drug interactions; heart cell; heart contraction; heart pharmacology; heart ventricle; isoproterenol; laboratory rat; myocardium; myofibrils; sarcoplasmic reticulum; single cell analysis; stimulant /agonist

The mechanical effects mediated by beta 2-adrenoceptor stimulation were studied in isolated rat ventricular myocytes. Beta 2-adrenoceptor stimulation was induced by using beta 2-selective agonist Zinterol and isoproterenol (ISO) in the presence of beta 1-selective antagonist CGP- 20712A. ICI was used as a selective beta 2-antagonist. Zinterol has an apparent positive inotropic effect which was associated with an increase in Cai transient. In addition, ISO in the presence of selective beta 1- blocker CGP-20712A has very similar effects on contraction and Cai transient. Both the effect of Zint and ISO can be antagonized by beta 2- blocker ICI 118,551, but not by CGP. Furthermore, the comparative data of beta 2 vs. beta 1-adrenoceptor stimulation show that there are some striking differences of cell responses to beta 1 and beta 2-adrenergic stimulation. For a given level of inotropic effect, beta 2 receptor stimulation has less effects on the time course of contraction and Cai transient on the myofilament sensitivity to Ca i, and is less arrhythmogenic than beta 1 receptor stimulation. These results demonstrate for the first time that in rat myocardium beta 2-adrenoceptors functionally coexist with beta 1-adrenoceptors and suggest that the cAMP stimulation by beta 1 and beta 2 may be compartmentalized or that beta 1 activates cellular mechanisms that offset the well-known cAMP-dependent action on the time course of contraction, Cai transient and on myofilament and sacroplasmic reticulum responsiveness to Ca 2+.

由β 2肾上腺素受体刺激介导的机械效应是 在分离的大鼠心室肌细胞中研究。 β 2肾上腺素受体 通过使用β 2-选择性激动剂锌特罗诱导刺激， 异丙肾上腺素（ISO）在β 1-选择性拮抗剂CGP- 20712A ICI用作选择性β 2-拮抗剂。 Zintrol具有 明显的正性肌力作用，这与增加 蔡瞬态。 此外，ISO在选择性β 1- 阻断剂CGP-20712 A对收缩和Cai的作用非常相似， 短暂的 Zint和ISO的作用均可被β 2-拮抗 阻断剂ICI 118，551，而不是CGP。 此外，比较数据 β 2与β 1肾上腺素受体刺激表明， 细胞对β 1和β 2-肾上腺素能的反应存在显著差异 刺激. 对于给定水平的变力作用，β 2受体 电刺激对收缩时程和Cai的影响较小， 瞬时对肌丝的敏感性Ca i， 比β 1受体刺激更易致炎。 这些结果证明 首次发现大鼠心肌β 2-肾上腺素能受体在功能上 与β 1-肾上腺素受体共存，并表明cAMP的刺激， β 1和β 2可能是区室化的，或者β 1激活 细胞机制，抵消了众所周知的cAMP依赖性作用， 收缩时程、Cai瞬变和肌丝， 骶浆网对Ca 2+的反应性。