پديد آورندگان :
GHASEMI-ZAD A. نويسنده , SADID A. نويسنده , ASGARI A. نويسنده , KHOSHBATEN A. نويسنده
چكيده لاتين :
Background: It has been suggested that organophosphates
may inhibit gamma-aminobutyric acid (GABA) metabolism in
synaptosomal preparations. In the present investigation, we
have assessed the interaction between paraoxon and the
GABA system at synaptic level.
Methods: Synaptosomes were prepared from male Wistar rats
(200-250 g). Cerebral cortex was dissected and homogenized,
then centrifuged at JOOOg for 5 min and again at 12000g for
20 min. The pellet containing synaptosomes was resuspended
in the buffer solution and the protein concentration adjusted at
I mg/ml. Determination of lactate dehydrogenase (LDH) activity,
as a biochemical index for synaptosomal integrity, was
assessed. Cholinesterase activity of synaptosomes was also
determined. Synaptosomes were preincubated for 20 min with
two concentrations of paraoxon (10. 9-1 0·3 M), and then incubated
with [3H]GABA for 10 min, before being washed
through 0.65 urn filters.
Results: Paraoxon inhibited cholinesterase activity ofsynaptosomes
in a concentration dependent manner. Synaptosomal
accumulation of [3H] GABA/GABA was time dependent and
peaked at 15 min. Paraoxon significantly increased the uptake
in nano molar concentrations and decreased it at higher
concentrations.
Conclusion: The result of this study indicate that in synaptosomes
prepared from rat cerebral cortex paraoxon increases
GABA uptake at low dose and inhibits its uptake at high doses.
This may imply a role for organophosphate-induced convulsion,
which needs further clarification.