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Information Seminar Paper

Title

PARAOXON INHIBITS [3H] GABA UPTAKE IN RAT BRAIN SYNAPTOSOMES

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Abstract

 Introduction: Parathion is an organophosphate compound that is frequently used as an insecticide. Paraoxon, the metabolic product of parathion, is reported to inhibit GABA uptake by rat cerebral cortex synaptosomes. The aim of this study is to investigate possible mechanism(s) underlying inhibitory effect of paraoxon on GABA uptake, in synaptosomes prepared from rat cerebral cortex.Methods: After preparation of synaptosomes kinetic studies were performed for determining the effect of paraoxon on Km and Vmax of GABA uptake. Acetylcholine and antagonists (atropine and mecamylamine) were used for evaluating cholinergic dependency of GABA uptake. Type of GABA transporter involved was determined by using glial (beta-alanine) and neuronal (L-DABA) GABA uptake inhibitors.Results: The results of the study showed that paraoxon significantly decreased Vmax (175.2±4.23 vs. 80.4±2.03 pmol/mg protein/min, P<0.001) of GABA uptake while had no effect on its Km (9.80±1.02 vs. 9.09±0.92μM in paraoxon and control groups respectively). DABA significantly decreased GABA uptake (P<0.001) while beta-alanine had no effect. Moreover, acetylcholine had no effect on GABA uptake. Furthermore, neither atropine nor mecamylamine could reverse the inhibitory effect of paraoxon on GABA uptake.Conclusion: In conclusion, present data suggests that paraoxon antagonizes kinetics of GABA uptake in nerve endings in a non-competitive manner. We also can conclude that the inhibitory effect of paraoxon on GABA uptake by rat cerebral synaptosomes is cholinergic-independent.

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