Carbachol induces a rapid and sustained hydrolysis of polyphosphoinositide in bovine tracheal smooth muscle measurements of the mass of polyphosphoinositides, 1,2-diacylglycerol, and phosphatidic acid.
Carbachol induces a rapid and sustained hydrolysis of polyphosphoinositide in bovine tracheal smooth muscle measurements of the mass of polyphosphoinositides, 1,2-diacylglycerol, and phosphatidic acid.
复制标题
DOI：
10.1016/s0021-9258(18)66923-6
复制
发表时间：
1986-11
期刊：
影响因子：
--
通讯作者：
Y. Takuwa;N. Takuwa;H. Rasmussen
中科院分区：
文献类型：
--
作者：
Y. Takuwa;N. Takuwa;H. Rasmussen
通过测量脂质质量和[3H]肌醇标记的磷酸肌醇的周转率，研究了卡巴胆碱对牛气管平滑肌中多磷酸肌醇和1,2-二酰甘油代谢的影响。卡巴胆碱诱导磷脂酰肌醇4,5-二磷酸和磷脂酰肌醇4-单磷酸的质量快速减少，以及1,2-二酰基甘油和磷脂酸的质量快速增加。这些脂质质量的变化持续至少 60 分钟。在 60 分钟的卡巴胆碱刺激期间，磷脂酰肌醇的水平显示出延迟性和渐进性的降低。添加阿托品可以完全逆转这些反应。卡巴胆碱刺激磷脂酰肌醇4,5-二磷酸和磷脂酰肌醇4-单磷酸中[3H]肌醇放射性的快速损失，这些放射性与[3H]肌醇三磷酸的产生有关。卡巴胆碱诱导的磷酸肌醇和磷脂酸质量的变化不受细胞外 Ca2+ 去除的影响，并且似乎不是继发于细胞内 Ca2+ 的增加。这些结果表明，卡巴胆碱引起磷脂酶C介导的多磷酸肌醇分解，导致三磷酸肌醇的产生和1,2-二酰基甘油的实际含量持续增加。这些结果强烈表明，卡巴胆碱诱导的收缩是通过多磷酸肌醇的水解介导的，从而产生两种信使：肌醇1,4,5-三磷酸和1,2-二酰基甘油。
The effects of carbachol on polyphosphoinositides and 1,2-diacylglycerol metabolism were investigated in bovine tracheal smooth muscle by measuring both lipid mass and the turnover of [3H]inositol-labeled phosphoinositides. Carbachol induces a rapid reduction in the mass of phosphatidylinositol 4,5-bisphosphate and phosphatidylinositol 4-monophosphate and a rapid increase in the mass of 1,2-diacylglycerol and phosphatidic acid. These changes in lipid mass are sustained for at least 60 min. The level of phosphatidylinositol shows a delayed and progressive decrease during a 60-min period of carbachol stimulation. The addition of atropine reverses these responses completely. Carbachol stimulates a rapid loss in [3H]inositol radioactivity from phosphatidylinositol 4,5-bisphosphate and phosphatidylinositol 4-monophosphate associated with production of [3H]inositol trisphosphate. The carbachol-induced change in the mass of phosphoinositides and phosphatidic acid is not affected by removal of extracellular Ca2+ and does not appear to be secondary to an increase in intracellular Ca2+. These results indicate that carbachol causes phospholipase C-mediated polyphosphoinositide breakdown, resulting in the production of inositol trisphosphate and a sustained increase in the actual content of 1,2-diacylglycerol. These results strongly suggest that carbachol-induced contraction is mediated by the hydrolysis of polyphosphoinositides with the resulting generation of two messengers: inositol 1,4,5-trisphosphate and 1,2-diacylglycerol.