Effect of GABA and isogabaculine on ornithine decarboxylase and putrescine metabolism

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Abstract
Isogabaculine, an irreversible inhibitor of GABA transaminase, when added to mouse neuroblastoma [C 1300] cells in spinner culture at the time of induction of cell proliferation, increased ornithine decarboxylase (ODC) activity > 3-fold that of normal control cells and > 2-fold that of GABA-treated cells. Isogabaculine did not affect ODC activity of rat glioma (C6) or rat hepatoma (HTC) cells. As determined by half-life measurements of ODC and intracellular GABA concentrations, isogamaculine apparently has a direct stabilizing effect on ODC in neuroblastoma cells that is unrelated to the accumulation of GABA due to GABA transaminase inhibition. Putrescine metabolism to GABA or spermidine was determined in C6, HTC and neuroblastoma cells in the presence or absence of isogabaculine and/or GABA. Neither GABA nor isogabaculine treatment dramatically altered the metabolism of putrescine to GABA or spermidine in neuroblastoma, C6 glioma or HTC cells. The appreciable amount of labeled GABA formed from putrescine indicated that this metabolic route may be more important than was previously thought.