Synaptosomal GABA uptake decreases in paraoxon-treated rat brain.
A synaptosomal model was used to evaluate in vivo effects of paraoxon on the uptake of [(3)H]GABA in rat cerebral cortex and hippocampus. Male Wistar rats were given a single intraperitoneal injection of one of three doses of paraoxon (0.1, 0.3, or 0.7 mg/kg) and acetylcholinesterase (AChE) activity in the plasma, cerebral cortex, and hippocampus was measured at 30 min, 4h, and 18 h after exposure. [(3)H]GABA uptake in synaptosomes was also studied in another series of animals. Paraoxon administration (0.3 and 0.7 mg/kg) caused significant inhibition of AChE activity in the plasma and both brain areas at all time points. 0.1 mg/kg paraoxon significantly inhibited AChE activity but only in the plasma for 4h, the activity was completely recovered at 18 h. GABA uptake was significantly (p<0.001) reduced in both cerebral cortex (18-32%) and hippocampal (16-23%) synaptosomes at all three time points after administering 0.7 mg/kg of paraoxon, a dose that seems to be sufficient to induce seizure activity. L-DABA, an inhibitor of neuronal GABA transporter, allowed us to conclude that the uptake was mediated primarily by neuronal GABA transporter GAT-1. In conclusion, present data suggests that GABA uptake by synaptosomes decreases probably secondary to paraoxon-induced seizure activity.
Mohammadi
Moslem
M
Department of Physiology and Biophysics, Baqiyatallah University of Medical Sciences, Tehran, Iran. Mohammadimo@yahoo.com
Ghani
Esmaeel
E
Ghasemi
Asghar
A
Khoshbaten
Ali
A
Asgari
Alireza
A
D000110:Acetylcholinesterase / Q000097:blood; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D002800:Cholinesterase Inhibitors / Q000633:toxicity; D003967:Diarrhea / Q000139:chemically induced; D004305:Dose-Response Relationship, Drug; D005207:Fasciculation / Q000139:chemically induced; D050485:GABA Plasma Membrane Transport Proteins / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009557:Nipecotic Acids / Q000494:pharmacology; D010261:Paraoxon / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D012472:Salivation / Q000187:drug effects; D013574:Synaptosomes / Q000187:drug effects* / Q000378:metabolism; D013666:Tears / Q000378:metabolism; D013997:Time Factors; D014202:Tremor / Q000139:chemically induced; D014316:Tritium; D014554:Urination / Q000187:drug effects; D015091:beta-Alanine / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism* / Q000493:pharmacokinetics
D002800:Cholinesterase Inhibitors; D050485:GABA Plasma Membrane Transport Proteins; D009557:Nipecotic Acids; D014316:Tritium; D015091:beta-Alanine; C030278:nipecotic acid; D005680:gamma-Aminobutyric Acid; D000110:Acetylcholinesterase; D010261:Paraoxon