GABA down-regulates the GABA/benzodiazepine receptor complex in developing cerebral neurons.
Neuronal cultures of the chick embryo cerebrum were used to study the chronic effects of gamma-aminobutyric acid (GABA) on the expression of the GABA/benzodiazepine receptor complex. A 7 day exposure of developing neurons to 100 microM GABA produced a 70% reduction in the level of [3H]flunitrazepam binding to intact cells, when compared to untreated controls. The reduction was due to a decrease in receptor density (Bmax) rather than the affinity. The same treatment also caused a 75% reduction in the rates of GABA-gated 36Cl- uptake by intact cells, without an effect on the basal (GABA-independent) flux. Eight days after removal of GABA from the medium of treated cultures, the neurons recovered [3H]flunitrazepam binding to levels corresponding to 74% of unexposed, age-matched controls. The results are consistent with a GABA-induced down-regulation of the GABA/benzodiazepine receptor.
Tehrani
M H
MH
Verna and Marrs McLean Department of Biochemistry, Baylor College of Medicine, Houston, TX 77030.
Barnes
E M
EM
D000818:Animals; D001921:Brain / Q000166:cytology / Q000196:embryology / Q000378:metabolism*; D002478:Cells, Cultured; D002642:Chick Embryo; D002712:Chlorides / Q000493:pharmacokinetics; D005445:Flunitrazepam / Q000378:metabolism; D007700:Kinetics; D011963:Receptors, GABA-A / Q000187:drug effects / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*
D002712:Chlorides; D011963:Receptors, GABA-A; D005680:gamma-Aminobutyric Acid; D005445:Flunitrazepam