Regulation of the GABAA receptor/ion channel complex by intracellular GABA levels.
Synaptosomes and synaptoneurosomes were prepared from the cerebral cortex of control rats and of rats treated with gabaculine, gamma-vinylGABA (GVG), hydrazine and isonicotinic acid hydrazide (INH). An inverse relationship was observed between the GABA content of the synaptoneurosomes and the muscimol-stimulated chloride ion uptake by the organelles. The relationship held over an extensive range of experimental conditions including different drugs, different dosage levels of the same drug, different time intervals after administration of the same drug, and both single and multiple injections of drugs. The results indicated that the phenomenon was associated with the neurosome component of the preparation, and raised the possibility that GABA levels within the postsynaptic cell might regulate the functioning of the GABAA receptor complex.
Wood
J D
JD
Department of Biochemistry, University of Saskatchewan, Saskatoon, Canada.
Davies
M
M
D000614:Aminocaproates / Q000494:pharmacology; D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D018118:Chloride Channels; D002712:Chlorides / Q000378:metabolism; D003509:Cyclohexanecarboxylic Acids / Q000494:pharmacology; D006834:Hydrazines / Q000494:pharmacology; D007538:Isoniazid / Q000494:pharmacology; D008297:Male; D008565:Membrane Proteins / Q000502:physiology*; D009118:Muscimol / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011963:Receptors, GABA-A / Q000502:physiology*; D013574:Synaptosomes / Q000378:metabolism; D020888:Vigabatrin; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D000614:Aminocaproates; D018118:Chloride Channels; D002712:Chlorides; D003509:Cyclohexanecarboxylic Acids; D006834:Hydrazines; D008565:Membrane Proteins; D011963:Receptors, GABA-A; D009118:Muscimol; C029424:hydrazine; C012987:gabaculine; D005680:gamma-Aminobutyric Acid; D020888:Vigabatrin; D007538:Isoniazid