Dassouli A, Sülpice J C, Roux S, Crozatier B
Unité INSERM U.2, Faculté de Médecine, Creteil, France.
J Mol Cell Cardiol. 1993 Aug;25(8):973-82. doi: 10.1006/jmcc.1993.1109.
The kinetics and signal transduction of inositol phosphate production were studied after a 20% stretch of neonatal rat cardiomyocytes in culture. Inositol trisphosphate (IP3) production was increased by 41% above control after 10-20 s of cellular stretch but returned to control after 120 s of stretch. The increase in IP3 was potentiated in high K+ medium and was inhibited by pertussis toxin, suggesting the existence of a pertussis toxin-sensitive G protein in signal transduction. Ion-pair HPLC analysis of cell extracts stretched for 20 s showed an increase in both IP3 isomers, mostly 1,4,5-IP3 (+66%) with a weak increase in IP4 (+10%), whereas 120 s stretch induced an increase in IP4 (+26% above control) associated with a decrease of 1,4,5-IP3 isomer as compared with 20 s stretch. It is concluded that the progressive increase in IP4 production associated with an early rise in IP3 after stretching myocardial cells may be a factor inducing the length-dependent activation of cardiac muscle through a modulation of intracellular free calcium concentration.
对培养的新生大鼠心肌细胞进行20%拉伸后，研究了肌醇磷酸生成的动力学和信号转导。细胞拉伸10 - 20秒后，三磷酸肌醇（IP3）生成量比对照增加了41%，但拉伸120秒后恢复到对照水平。在高钾培养基中，IP3的增加得到增强，且被百日咳毒素抑制，这表明在信号转导中存在一种对百日咳毒素敏感的G蛋白。对拉伸20秒的细胞提取物进行离子对高效液相色谱分析显示，两种IP3异构体均增加，主要是1,4,5 - IP3（增加66%），IP4略有增加（增加10%），而拉伸120秒诱导IP4增加（比对照高26%），与拉伸20秒相比，1,4,5 - IP3异构体减少。结论是，拉伸心肌细胞后，IP4生成的逐渐增加与IP3的早期升高相关，这可能是通过调节细胞内游离钙浓度诱导心肌长度依赖性激活的一个因素。
