Differential Inhibitory Effects of 2-Azafluorenones on PI-PLC Activation but not on PC-PLC- or PC-PLD-Activation Induced by Histamine, PAF, PMA or A23187 in C6 Glioma Cells

作者：Wang Hai Long; Wang Li Chuan; Wei Jiann Wu^*

来源：Chinese Journal of Physiology, 2013, 56(1): 11-17.

DOI：10.4077/CJP.2013.BAA073

• 2-azafluorenones
• PI-PLC activation
• IP1 formation
• histamine
• PAF
• PMA

In this study, C6 glioma cells were used to test the effects of 2-azafluorenone and its related compounds on membrane phosphatidylinositol (PI) and phosphatidylcholine (PC) turnover. An increase of [H-3]-labeled inositol phosphate (IP1) formation by histamine (100 mu M) or A23187 (100 nM) via the activation of phosphatidylinositol-specific phospholipase C (PI-PLC) to breakdown labeled substrate was observed, and this effect could be partially blocked by about half at 100 mu M of 2-azafluorenones. Histamine induced the increase of IP1 formation, but failed to cause an increase in extracellularly releasing of [H-3]choline metabolites, or intracellular accumulation of [H-3]phosphocholine. However, platelet activation factor (PAF) from 0.2 to 1 mu M, and phorbol 12-myristate-13-acetate (PMA) at 1 mu M caused an increase in extracellularly releasing of [H-3]choline metabolites, and intracellular accumulation of [H-3]phosphocholine via the activation on phosphatidylcholine (PC)-PLC. These responses of PAF and PMA were not affected by 2-azafluorenone or 4-methy1-2-azafluorenone even at high concentration (10(-4) M). A23187 induced an increase of intracellular [H-3]choline release via the activation of PC-phospholipase D (PLD). This increasing effect of 100 nM A23187 was not affected by 2-azafluorenone or 4-methy1-2-azafluorenone even at a high concentration of 10(-4) M. In summary, the inhibitory effect of 2-azafluorenone and its related compound 4-methy1-2-azafluorenone was observed selectively on PIPLC, but not on PC-PLC or PC-PLD based on changes of products after the activation of these enzymes.

• 出版日期2013-2-28