The effect of acetylcholinesterase-inhibition on depolarization-induced GABA release from rat striatal slices.
The severity of poisoning after intoxication with the acetylcholinesterase (AChE) inhibitor soman has been shown to be positively correlated with GABA release in rat striatum. Since most of the neurons in striatum and striatal projection regions use GABA as transmitter, it is still unclear, whether an increase of extracellular GABA in this region results from enhanced activation of these projections or is due to the local effect of AChE inhibition. In this study, the modulation of depolarization-induced increase in GABA concentration by soman was determined in the superfusate of rat striatal slices. Soman and neostigmine increased GABA concentration in the superfusate dose dependently. This increase was exerted through M-cholinoceptors as it could be blocked by atropine and enhanced by application of the muscarinic agonists pilocarpine or oxotremorine. These results clearly indicate that AChE inhibition by soman in rat striatum can directly lead to enhanced release of GABA through M-cholinoceptors.
Grasshoff
Christian
C
Institute of Pharmacology and Toxicology, German Armed Forces Medical Academy, Muenchen, Germany. christian.grasshoff@t-online.de
Gillessen
Thomas
T
Thiermann
Horst
H
Wagner
Erwin
E
Szinicz
Ladislaus
L
D000110:Acetylcholinesterase / Q000378:metabolism*; D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002800:Cholinesterase Inhibitors / Q000633:toxicity*; D002851:Chromatography, High Pressure Liquid; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D018721:Muscarinic Agonists / Q000494:pharmacology; D009388:Neostigmine / Q000633:toxicity; D017072:Neostriatum / Q000187:drug effects / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects; D018722:Nicotinic Agonists / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012999:Soman / Q000633:toxicity; D013050:Spectrometry, Fluorescence; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D002800:Cholinesterase Inhibitors; D018721:Muscarinic Agonists; D018722:Nicotinic Agonists; D009388:Neostigmine; D005680:gamma-Aminobutyric Acid; D012999:Soman; D000110:Acetylcholinesterase