Response of cardiac myocytes to a ramp increase of diacylglycerol generated by photolysis of a novel caged diacylglycerol.
Response of cardiac myocytes to a ramp increase of diacylglycerol generated by photolysis of a novel caged diacylglycerol.
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心肌细胞对新型笼状二酰甘油光解产生的二酰甘油斜坡增加的反应。
DOI：
10.1016/s0006-3495(96)79816-8
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发表时间：
1996
期刊：
影响因子：
--
通讯作者：
Walker,JW
中科院分区：
文献类型：
--
作者：
Huang,XP;Sreekumar,R;Patel,JR;Walker,JW
为了测试活细胞对细胞内信使二酰甘油的反应性，我们开发了一个原型笼状二酰甘油化合物，3-O-(α-羧基-2，4-二硝基苄基)-1，2-二辛酰基-RAC-甘油(命名为α-羧基笼状DIC(8))，它在光解过程中产生二辛酰甘油(DIC(8))。α-羧基笼状DIC(8)在体外对二酰基甘油激酶和蛋白激酶C是生物惰性的，并且很容易被结合到心肌细胞膜上，在那里它在照射前没有作用。暴露在近紫外光下，以良好的产率(量子效率=0.2)释放生物活性的diC8。在这里，我们研究了单个心肌细胞内对diC8受控升高的细胞反应。在电刺激的心肌细胞中监测到抽动幅度，并通过持续照射装入笼状化合物的细胞产生陡峭的DIC(8)浓度增加。心肌细胞的反应是两相的，先是正性肌力相(痉挛幅度增加39%)，然后是大负性肌力相(>；减少80%)。随着光照强度的增加，各向异性达到峰值的时间从376+/-51 S减少到44+/-5 S(正相)和422+/-118 S减少到51+/-9 S(负相)。这两个时相都被蛋白激酶C抑制剂氯化胆碱抑制。细胞外K+从5 mM增加到20 mM以部分去极化细胞膜，消除了正性肌力相，但负性肌力反应基本没有改变。结果揭示了心肌对二酰甘油反应的新特征，包括正性变力阶段和对二酰甘油简单线性增加的复杂反应。光释放DIC(8)的作用类似于选择kappa受体的阿片激动剂的作用，与二酰甘油在这些反应中的主要作用一致。
To test the responsiveness of living cells to the intracellular messenger diacylglycerol, we developed a prototype caged diacylglycerol compound, 3-O-(alpha-carboxyl-2,4-dinitrobenzyl)-1 ,2-dioctanoyl-rac-glycerol (designated alpha-carboxyl caged diC(8)), that produces dioctanoylglycerol (diC(8)) on photolysis. Alpha-Carboxyl caged diC(8) is biologically inert toward diacylglycerol kinase and protein kinase C in vitro and is readily incorporated into cardiac myocyte membranes, where it has no effect before irradiation. Exposure to near-UV light releases biologically active diC8 in good yield (quantum efficiency=0.2). Here we examine a cellular response to controlled elevation of diC8 within single cardiac myocytes. Twitch amplitude was monitored in electrically stimulated myocytes, and a ramp increase in the concentration of diC(8) was generated by continuous irradiation of cells loaded with the caged compound. The myocyte response was biphasic with a positive inotropic phase (39% increase in twitch amplitude), followed by a large negative inotropic phase (>80% decrease). The time to peak inotropy for both phases depended on the light intensity, decreasing from 376 +/- 51 S to 44 +/- 5 s (positive phase) and 422 +/- 118 S to 51 +/- 9 S (negative phase) as the light intensity was increased eightfold. Both phases were inhibited by the protein kinase C inhibitor chelethyrine chloride. An increase in extracellular K+ from 5 mM to 20 mM to partially depolarize the cell membrane eliminated the positive inotropic phase, but the negative inotropic response was largely unaltered. The results reveal new features in the response of cardiac muscle to diacylglycerol, including a positive inotropic phase and a complex responsiveness to a simple linear increase in diacylglycerol. The effects of photoreleased diC(8) were similar to the effects of opiate agonists selective for kappa receptors, consistent with a major role for diacylglycerol in these responses.
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DOI：
--
发表时间：
1985
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Davis,RJ;Ganong,BR;Bell,RM;Czech,MP
通讯作者：
Czech,MP
DOI：
10.1073/pnas.83.5.1184
发表时间：
1986-03-01
影响因子：
11.1
作者：
GANONG, BR;LOOMIS, CR;BELL, RM
通讯作者：
BELL, RM
蛋白激酶 C 抑制剂和 Na +/H + 交换对大鼠左心室乳头肌 α1 肾上腺素受体介导的正性肌力反应的影响
影响因子：
7.3
作者：
H. Otani;H. Otani;Toshiko Uriu;M. Hara;M. Inoue;K. Omori;E. Cragoe;C. Inagaki
通讯作者：
C. Inagaki
促肿瘤佛波醇酯在灌注跳动的大鼠心脏中抑制心脏功能并诱导蛋白激酶 C 重新分布
影响因子：
20.1
作者：
S. Yuan;F. Sunahara;A. K. Sen
通讯作者：
A. K. Sen
佛波酯对培养鸡心脏细胞收缩状态和钙通量的影响。
DOI：
10.1152/ajpheart.1987.253.1.h205
发表时间：
1987
期刊：
The American journal of physiology
影响因子：
--
作者：
Leatherman,GF;Kim,D;Smith,TW
通讯作者：
Smith,TW