Paraoxon inhibits GABA uptake in brain synaptosomes

To investigate possible effect of paraoxon (10−9–10−3 M) on GABA uptake, we used rat cerebral cortex synaptosomes. Km and Vmax of GABA uptake were determined in presence of paraoxon (10−3 M). Acetylcholine and its antagonists (atropine and mecamylamine) were used for evaluating cholinergic-dependency of uptake. Type of transporter involved was determined by using glial (beta-alanine) and neuronal (DABA) GABA uptake inhibitors. The results of the study showed that paraoxon at low doses (10−9–10−6 M) increased and at high doses (10−5–10−3 M) decreased GABA uptake. One millimolar paraoxon significantly decreased Vmax (175.2 ± 4.23 vs. 80.4 ± 2.03, P < 0.001) of GABA uptake while had no effect on its Km. DABA significantly decreased GABA uptake (P < 0.001) while beta-alanine had no effect. In conclusion, present data suggests that paraoxon probably acts as non-competitive antagonist of GABA uptake.