Jope R S
Department of Pharmacology and Neuropsychiatry Research Program, University of Alabama, Birmingham.
J Neurochem. 1988 Dec;51(6):1731-6. doi: 10.1111/j.1471-4159.1988.tb01152.x.
NaF stimulated phosphoinositide hydrolysis in rat cortical slices. The production of [3H]inositol monophosphate was rapid for the first 15 min of incubation with NaF, followed by a plateau. The major product detected was [3H]inositol monophosphate, although significant amounts of [3H]inositol bisphosphate and [3H]inositol trisphosphate were also produced. The stimulation of [3H]inositol monophosphate production by NaF was concentration dependent between 2 and 20 mM NaF. Addition of 10 or 100 microM AlCl3 or aluminum maltol did not alter the effect of NaF, whereas at 500 microM, these aluminum preparations resulted in significant inhibition. Increasing the concentration of K+ from 5 to 20 mM potentiated [3H]inositol monophosphate production induced by carbachol but not by NaF. Incubation with 1 microM phorbol 12-myristate 13-acetate, a phorbol ester, inhibited carbachol-induced, but not NaF-induced, [3H]inositol monophosphate production. These results further support the hypothesis that a guanine nucleotide binding protein that can be activated by NaF is involved in phosphoinositide hydrolysis in brain. The use of NaF provides a means to bypass receptors to study intracellular regulatory sites of phosphoinositide metabolism without disrupting cells.
氟化钠刺激大鼠皮层切片中的磷酸肌醇水解。与氟化钠孵育的最初15分钟内，[3H]肌醇单磷酸的生成迅速，随后趋于平稳。检测到的主要产物是[3H]肌醇单磷酸，不过也生成了大量的[3H]肌醇二磷酸和[3H]肌醇三磷酸。在2至20 mM氟化钠浓度范围内，氟化钠对[3H]肌醇单磷酸生成的刺激呈浓度依赖性。添加10或100 μM三氯化铝或麦芽醇铝不会改变氟化钠的作用，而在500 μM时，这些铝制剂会导致显著抑制。将钾离子浓度从5 mM提高到20 mM可增强卡巴胆碱诱导的[3H]肌醇单磷酸生成，但对氟化钠诱导的无此作用。用1 μM佛波醇12 - 肉豆蔻酸酯13 - 乙酸酯（一种佛波酯）孵育可抑制卡巴胆碱诱导的[3H]肌醇单磷酸生成，但不影响氟化钠诱导的生成。这些结果进一步支持了以下假说：一种可被氟化钠激活的鸟嘌呤核苷酸结合蛋白参与了脑中磷酸肌醇的水解。使用氟化钠提供了一种绕过受体来研究磷酸肌醇代谢细胞内调节位点而不破坏细胞的方法。
