Effect of gamma-vinyl gamma-aminobutyric acid on the gamma-aminobutyric acid receptor-coupled chloride ion channel in vesicles from the brain of the rat.
The effect of gamma-vinyl GABA on the gamma-aminobutyric acid (GABA) receptor-coupled chloride ion (Cl-) channel was studied using membrane vesicles from cerebral cortex of the rat. gamma-Vinyl GABA, an antiepileptic drug, had no effect on uptake of 36Cl-, without preincubation. However, preincubation of membrane vesicles with gamma-vinyl GABA (100-1000 microM) produced a concentration-dependent decrease in net uptake of 36Cl-. No alteration was observed in basal uptake of 36Cl-. This decrease in net uptake of 36Cl- was not related to desensitization induced by endogenous GABA, which might be increased by gamma-vinyl GABA through selective, irreversible inhibition of GABA-transaminase (GABA-T). Concentration-response curves for GABA showed that preincubation with gamma-vinyl GABA inhibited GABA-stimulated uptake of 36Cl- with no change in ED50. These results indicate that gamma-vinyl GABA may act directly at the GABA/benzodiazepine ionophore complex, as a non-competitive antagonist of GABA.
Suzuki
Y
Y
Department of Pediatrics, Osaka University Medical School, Japan.
Mimaki
T
T
Arai
H
H
Okada
S
S
Kuriyama
K
K
D000612:4-Aminobutyrate Transaminase / Q000037:antagonists & inhibitors*; D000614:Aminocaproates / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000378:metabolism*; D018118:Chloride Channels; D002712:Chlorides / Q000378:metabolism*; D066298:In Vitro Techniques; D007477:Ions; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D008566:Membranes / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011963:Receptors, GABA-A / Q000187:drug effects*; D013997:Time Factors; D020888:Vigabatrin
D000614:Aminocaproates; D018118:Chloride Channels; D002712:Chlorides; D007477:Ions; D008565:Membrane Proteins; D011963:Receptors, GABA-A; D000612:4-Aminobutyrate Transaminase; D020888:Vigabatrin