Involvement of polyamine acetylation in pentylenetetrazol-induced kindling

研究了大鼠大脑多个区域中多胺（腐胺、亚精胺和精胺）、乙酰多胺（N^1-乙酰亚精胺和N^1-乙酰精胺）和γ-氨基丁酸（GABA）的浓度，其中通过重复注射戊四氮（PTZ ; 33或40 mg/kg/2或3天，腹腔注射）诱导化学点燃。在点燃大鼠，腐胺水平增加后8和24小时，最后PTZ注射。腐胺的增加率在脑区之间有显着差异，在大脑皮层中检测到最显着的增加。亚精胺和精胺水平没有增加，在任何大脑区域检查。这些结果表明，大脑皮层可能是最活跃的区域在PTZ点燃的大脑中至少在最后一次注射后8小时。用多胺氧化酶抑制剂MDL 72，527预处理，诱导乙酰多胺的积累。点燃惊厥后，乙酰多胺水平升高16小时后，最后PTZ注射，特别是在大脑皮层，多胺乙酰化的激活。与此相反，腐胺和GABA的水平下降，在MDL预处理点燃大鼠。正常小鼠和大鼠经MDL 72，527处理后，癫痫发作阈值均下降，说明PTZ对某些脑区，特别是大脑皮层的选择性和重复性兴奋是诱发PTZ点燃的关键事件。多胺乙酰化活性升高可能与高兴奋性点燃脑内抑制因子腐胺和GABA的供应有关。

Concentrations of polymines (putrescine, spermidine, and spermine), acetylpolyamines (N^1-acetylspermidine and N^1-acetylspermine), and gamma-aminobutyric acid (GABA) were investigated in several regions of rat brain, in which chemical kindling was induced by repeated injection of pentylenetetrazol (PTZ ; 33 or 40 mg/kg/2 or 3 days, i.p.). In kindled rats, the putrescine levels increased 8 and 24 h after the final PTZ injection. The rates of putrescine increase were significantly different among brain regions and the most marked increase was detected in the cerebral cortex. Spermidine and spermine levels did not increase in any brain regions examined. These results indicate that the cerebral cortex may to be the most activated region in PTZ-kindled brain at least by 8 h after the final injection. Pretreatment with polyamine oxidase inhibitor, MDL 72,527, induced the accumulation of acetylpolyamines. After kindling convulsion, levels of acetylpolyamines were elevated 16 h after the final PTZ injection, especially in the cerebral cortex, showing the activation of polyamine acetylation. In contrast, levels of putrescine and GABA were decreased in the MDL-pretreated kindled rats. The seizure thresholds were down after the treatment of MDL 72,527 in normal mice and rats.In conclusion, the selective and repeated excitation by PTZ in some restricted brain regions, particularly in the cerebral cortex, appear to be critical events for the induction of PTZ kindling. Elevated activity of polyamine acetylation may be associated with the supply of putrescine and GABA,the inhibitory factors, in hyperexcited kindled brain.