Breakdown of polyphosphoinositides and not phosphatidylinositol accounts for muscarinic agonist-stimulated inositol phospholipid metabolism in rat parotid glands.
Breakdown of polyphosphoinositides and not phosphatidylinositol accounts for muscarinic agonist-stimulated inositol phospholipid metabolism in rat parotid glands.
复制标题
多磷酸肌醇的分解而不是磷脂酰肌醇的分解解释了大鼠腮腺中毒蕈碱激动剂刺激的肌醇磷脂代谢。
DOI：
10.1042/bj2160633
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发表时间：
1983
期刊：
影响因子：
--
通讯作者：
M. Wusteman
中科院分区：
文献类型：
--
作者：
C. Downes;M. Wusteman
使用预先标记有示踪剂量的[3 H]肌醇的大鼠腮腺切片，然后用10 mM未标记的肌醇洗涤，研究了毒蕈碱激动剂增强肌醇磷脂代谢能力的分子机制。卡巴胆碱治疗引起放射性肌醇1-磷酸，肌醇1，4-二磷酸，肌醇1，4，5-三磷酸的水平迅速和显着的增加，并在游离肌醇池中的标记的积累。[3 H]磷脂酰肌醇、[3 H]磷脂酰肌醇4-磷酸和[3 H]磷脂酰肌醇4，5-二磷酸水平的变化要小得多。卡巴胆碱刺激后5 s，[3 H]肌醇1，4-二磷酸和[3 H]肌醇1，4，5-三磷酸大量增加，但[3 H]肌醇1-磷酸没有增加。在用卡巴胆碱刺激10分钟后，放射性肌醇1，4-二磷酸和肌醇1，4，5-三磷酸的水平分别大大超过磷脂酰肌醇4-磷酸和磷脂酰肌醇4，5-二磷酸的起始放射性水平。当卡巴胆碱治疗后加入足够的阿托品阻断所有的毒蕈碱受体的放射性肌醇磷酸迅速返回到控制水平。卡巴胆碱诱发的放射性磷酸肌醇和磷脂水平的变化被阻断在2，4-二硝基苯酚（氧化磷酸化解偶联剂）的存在下。结果表明，毒蕈碱激动剂刺激多磷酸肌醇特异性磷脂酶C，这些脂质不断补充标记的磷脂酰肌醇池。[3 H]受刺激腺体中的肌醇1-磷酸可能通过肌醇1，4-二磷酸水解而产生，而不是直接来自磷脂酰肌醇。
The molecular mechanisms underlying the ability of muscarinic agonists to enhance the metabolism of inositol phospholipids were studied using rat parotid gland slices prelabelled with tracer quantities of [3H]inositol and then washed with 10 mM unlabelled inositol. Carbachol treatment caused rapid and marked increases in the levels of radioactive inositol 1-phosphate, inositol 1,4-bisphosphate, inositol 1,4,5-trisphosphate and an accumulation of label in the free inositol pool. There were much less marked changes in the levels of [3H]phosphatidylinositol, [3H]phosphatidylinositol 4-phosphate and [3H]phosphatidylinositol 4,5-bisphosphate. At 5 s after stimulation with carbachol there were large increases in [3H]inositol 1,4-bisphosphate and [3H]inositol 1,4,5-trisphosphate, but not in [3H]inositol 1-phosphate. After stimulation with carbachol for 10 min the levels of radioactive inositol 1,4-bisphosphate and inositol 1,4,5-trisphosphate greatly exceeded the starting level of radioactivity in phosphatidylinositol 4-phosphate and phosphatidylinositol 4,5-bisphosphate respectively. When carbachol treatment was followed by addition of sufficient atropine to block all the muscarinic receptors the radioactive inositol phosphates rapidly returned towards control levels. The carbachol-evoked changes in radioactive inositol phosphate and phospholipid levels were blocked in the presence of 2,4-dinitrophenol (an uncoupler of oxidative phosphorylation). The results suggest that muscarinic agonists stimulate a polyphosphoinositide-specific phospholipase C and that these lipids are continuously replenished from the labelled phosphatidylinositol pool. [3H]Inositol 1-phosphate in the stimulated glands probably arises via hydrolysis of inositol 1,4-bisphosphate and not directly from phosphatidylinositol.