Pretreatment with pertussis toxin blocks the protective effects of preconditioning: evidence for a G-protein mechanism.
Pretreatment with pertussis toxin blocks the protective effects of preconditioning: evidence for a G-protein mechanism.
复制标题
百日咳毒素预处理可阻断预处理的保护作用：G 蛋白机制的证据。
DOI：
10.1006/jmcc.1993.1037
复制
发表时间：
1993
影响因子：
5
通讯作者：
Downey,JM
中科院分区：
文献类型：
--
作者：
Thornton,JD;Liu,GS;Downey,JM
我们测试了百日咳毒素敏感的G蛋白是否介导预处理的保护作用。使用了31只小型（1 kg）家兔。所有家兔均经历30 min局部心肌缺血，随后3 h再灌注。用四唑盐法测定晶体大小。对照组梗死危险区的百分比为37.4 ± 4.6%。在30分钟缺血损伤之前，先进行5分钟闭塞，然后再进行10分钟再灌注的预处理可防止梗死（5.2 ± 2.1%梗死）。手术前48小时给予25 μg/kg百日咳毒素，通过iv乙酰胆碱（通常减慢心脏）激发试验，阻断G蛋白信号转导。百日咳毒素处理对非预处理兔的梗死面积（37.6 ± 4.7%梗死）没有影响，但阻断了预处理兔的保护作用（27.3 ± 4.3%梗死）。为了进一步测试G蛋白在预处理中的参与，我们测试了M2激动剂卡巴胆碱替代缺血预处理和保护心脏免于梗死的能力。离体兔心脏，用Kreb缓冲液灌注。对照组动物局部缺血30分钟，再灌注2小时，梗死发生率为29.4 ± 2.9%。缺血5 min再灌注10 min后再局部缺血30 min，心肌梗死率为8.41 ± 3.26%。1 μM卡巴胆碱灌注5 min，心肌梗死发生率为8.90 ± 2.08%。我们的结论是，预处理涉及百日咳毒素敏感的G蛋白和相同的G蛋白夫妇的毒蕈碱M2受体。
We tested whether a pertussis toxin-sensitive G-protein mediates the protective effects of preconditioning. Thirty-one small (1 kg) rabbits were used. All rabbits experienced 30 min regional myocardial ischaemia followed by 3 h reperfusion. Infarct size was determined by tetrazolium. The percentage of the risk zone which infarcted in controls was 37.4 ± 4.6%. Preconditioning with a 5 min occlusion followed by 10 min reperfusion prior to the 30 min ischaemic insult protected against infarction (5.2 ± 2.1% infarction). 25 μg/kg pertussis toxin, administered 48 h prior to surgery, blocked G-protein signal transduction as tested by challenge with iv acetylcholine which normally slows the heart. Pertussis toxin treatment had no effect on infarct size in non-preconditioned rabbits (37.6 ± 4.7% infarction) but blocked protection in preconditioned rabbits (27.3 ± 4.3% infarction). To test the involvement of G-proteins further in preconditioning, we tested the ability of the M2 agonist carbachol to substitute for ischaemic preconditioning and protect the heart from infarction. Rabbits hearts were excised and perfused with Kreb's buffer. Control animals subjected to 30 min of regional ischaemia and 2 h reperfusion yielded 29.4 ± 2.9% infarction. Preconditioning with 5 min global ischaemia and 10 min reperfusion prior to the 30 min regional ischaemia significantly protected the isolated heart from infarction (8.41 ± 3.26% infarction). Carbachol, infused for 5 min at 1 μM concentration, protected the hearts as well as preconditioning, yielding 8.90 ± 2.08% infarction. We concluded that preconditioning involves a pertussis toxin-sensitive G-protein and that the same G-protein couples to muscarinic M2 receptors.