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Methods for the Discovery of Novel Compounds Modulating a Gamma-Aminobutyric Acid Receptor Type A Neurotransmission
Published on: August 16, 2018
In vitro assessment of paraoxon effects on GABA uptake in rat hippocampal synaptosomes
Fereshteh Pourabdolhossein1, Asghar Ghasemi, Ameneh Shahroukhi
1Department of Physiology, School of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
Abstract:
Treating organophosphate poisoning is achieved mainly using compounds with anticholinergic characteristics. Nevertheless currently the focus of attention is aimed at examining their interference with other neurotransmitter systems. The present investigation studied the potential interactions between paraoxon and GABA uptake in hippocampal synaptosomes. Wistar rats weighing 200-250 g were used. Hippocampal synaptosomes were prepared and incubated with [(3)H] GABA in the presence of different doses of paraoxon for 10 min at 37 degrees C; and were then layered in chambers of a superfusion system and the [(3)H] GABA uptake was measured. Our finding revealed that mean GABA uptake decreased by 21%, 42%, 37%, 20%, and 8% of the corresponding control values in the presence of paraoxon concentrations of 0.01, 0.1, 1, 10, and 100 microM, respectively which was significant at 0.1 and 1 microM of paraoxon (P<0.05). In conclusion, micromolar concentrations of paraoxon were shown to interfere with GABA uptake in hippocampal synaptosomes, which indicates the GABA transporters may play a role in organophosphate-induced convulsions.