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. K(m) and V(max) 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 V(max) (175.2+/-4.23 vs. 80.4+/-2.03, P<0.001) of GABA uptake while had no effect on its K(m). 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.