Involvement of polyamine acetylation in pentylenetetrazol-induced kindling

本文研究了多次注射戊四氮(PTZ，33或40 mg/kg/2或3天)化学点燃大鼠脑内多胺(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。在点燃大鼠，末次注射PTZ后8小时和24小时，腐胺水平升高。腐胺的增加速度在不同的脑区有显着差异，其中大脑皮层的增加最为明显。在被检查的任何大脑区域中，精胺和精胺水平都没有增加。这些结果表明，至少在最后一次注射后8h，大脑皮层可能是PTZ点燃脑中最活跃的区域。多胺氧化酶抑制剂MDL 72,527可诱导乙酰多胺的积累。点燃惊厥后，末次注射PTZ后16h，大脑皮层中乙酰多胺水平明显升高，表现为多胺乙酰化的激活。相反，MDL处理的点燃大鼠的腐胺和GABA水平降低。经MDL 72,527处理后，正常小鼠和大鼠的惊厥阈值降低。结论：PTZ在某些受限的脑区，特别是大脑皮层的选择性和重复兴奋，似乎是诱发PTZ点燃的关键事件。多胺乙酰化活性的升高可能与高兴奋点燃脑中抑制因子腐胺和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.