Involvement of polyamine acetylation in pentylenetetrazol-induced kindling

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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.