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Mechanism of Paraoxon Effect on [3H] GABA Uptake Inhibition in Brain Synaptosomes of Rat
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Ghasemi A *   , Sadidi A , Mohammadi M , Khoshbaten A , Asgari AR |
| , Ghasemi@erc.ac.ir |
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Abstract: (11899 Views) |
| Background: Parathion is an organophosphate compound that is frequently used as an insecticide. Paraoxon is the metabolic product of parathion which previously reported that inhibits GABA uptake by rat cerebral cortex synaptosomes. The aim of this study is to investigate possible underlying inhibitory mechanism(s) of paraoxon on GABA uptake, in synaptosomes prepared from rat cerebral cortex. Materials and Methods: After preparation of synaptosomes, kinetic studies were performed to determe the effect of paraoxon on Km and Vmax of GABA uptake. Acetylcholine and its antagonists (atropine and mecamylamine) were used to evaluate cholinergic dependency of GABA uptake. Type of GABA transporter involved was determined using beta-alanine and DABA. 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. Acetylcholine had no effect on GABA uptake. On the other hand, neither atropine nor mecamylamine could reverse the inhibitory effect of paraoxon on GABA uptake. Conclusion: In conclusion, it seems that paraoxon acts as non-competitive anatagonist of GABA uptake, which affects kinetics of GABA uptake in nerve endings. We also conclude that the inhibitory effect of paraoxon on GABA uptake is cholinergic-independent |
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| Keywords: Paraoxon, Synaptosome, GABA uptake, Vmax, Km, Organophosphorus compounds |
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Full-Text [PDF 141 kb]
(1714 Downloads)
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Type of Study: Original |
Subject:
Medicine
Received: 2017 | Accepted: 2017 | Published: 2017
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