Acetylcholine but not adenosine triggers preconditioning through PI3-kinase and a tyrosine kinase.
Acetylcholine but not adenosine triggers preconditioning through PI3-kinase and a tyrosine kinase.
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DOI：
10.1152/ajpheart.00476.2002
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发表时间：
2003-02
期刊：
影响因子：
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通讯作者：
Qining Qin;J. Downey;M. Cohen
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文献类型：
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作者：
Qining Qin;J. Downey;M. Cohen
腺苷和乙酰胆碱通过不同的信号通路触发预适应。磷脂酰肌醇3-激酶（PI 3-激酶），一种蛋白酪氨酸激酶，和Src家族酪氨酸激酶参与预处理在离体兔心脏进行了评价。给予渥曼青霉素（PI 3-激酶阻断剂）、染料木黄酮（酪氨酸激酶阻断剂）、拉古斯汀A（酪氨酸激酶阻断剂）或4-氨基-5-（4-氯苯基）-7-（叔丁基）吡唑并[3，4-d]嘧啶（PP 2; Src家族酪氨酸激酶阻断剂）15分钟，以包括5分钟腺苷或ACh输注（触发阶段）。然后心脏进行30分钟的局部缺血。ACh单独给药的脑梗死面积为危险区的9.3 ± 3.5%，对照组为34.3 ± 4.1%。所有四种抑制剂阻断乙酰胆碱诱导的保护。当渥曼青霉素或PP 2仅在30分钟的缺血期（介质阶段）输注时，ACh诱导的保护不受影响（分别为7.4 +/- 2.1%和9.7 +/- 1.7%梗死）。腺苷触发的保护作用不被任何抑制剂阻断。因此，PI 3-激酶和至少一种蛋白酪氨酸激酶，可能是Src激酶，参与ACh诱导的触发相，但不是腺苷诱导的预处理。PI 3-激酶和Src激酶均不是ACh保护作用的介导者。
Adenosine and acetylcholine (ACh) trigger preconditioning by different signaling pathways. The involvement of phosphatidylinositol 3-kinase (PI3-kinase), a protein tyrosine kinase, and Src family tyrosine kinase in preconditioning was evaluated in isolated rabbit hearts. Either wortmannin (PI3-kinase blocker), genistein (tyrosine kinase blocker), lavendustin A (tyrosine kinase blocker), or 4-amino-5-(4-chlorophenyl)-7-(t-butyl)pyrazolol[3,4-d]pyrimidine (PP2; Src family tyrosine kinase blocker) was given for 15 min to bracket a 5-min infusion of either adenosine or ACh (trigger phase). The hearts then underwent 30 min of regional ischemia. Infarct size for ACh alone was 9.3 +/- 3.5% of the risk zone versus 34.3 +/- 4.1% in controls. All four inhibitors blocked ACh-induced protection. When wortmannin or PP2 was infused only during the 30-min ischemic period (mediator phase), ACh-induced protection was not affected (7.4 +/- 2.1% and 9.7 +/- 1.7% infarction, respectively). Adenosine-triggered protection was not blocked by any of the inhibitors. Therefore, PI3-kinase and at least one protein tyrosine kinase, probably Src kinase, are involved in the trigger phase of ACh-induced, but not adenosine-induced, preconditioning. Neither PI3-kinase nor Src kinase is a mediator of the protection of ACh.