Increased binding of [3H]muscimol and [3H]flunitrazepam in the rat brain under hypoxia.
We examined the effects of in vivo hypoxia (10% O2/90% N2) on the gamma-aminobutyric acid (GABA)/benzodiazepine receptors and on glutamic acid decarboxylase (GAD) activity in the rat brain. Male Wistar rats were exposed to a mixture of 10% O2 and 90% N2 in a chamber for various periods (3, 6, 12, and 24 h). The control rats were exposed to room air. The brain regions examined were the cerebral cortex, striatum, hippocampus, and cerebellum. GABA and benzodiazepine receptors were assessed using [3H]muscimol and [3H]flunitrazepam, respectively. Compared with control values, GAD activity was decreased significantly following a 6-h exposure to hypoxia in all four regions studied. On the other hand, the numbers of both [3H]muscimol and [3H]flunitrazepam binding sites were increased significantly. The increase in receptor number tended to return to control values after 24 h. Treatment of the membrane preparations with 0.05% Triton X-100 eliminated the increase in the binding capacity. These results may represent an up-regulation of postsynaptically located GABA/benzodiazepine receptors corresponding to the impaired presynaptic activity under hypoxia.
Ninomiya
H
H
Department of Pharmacology, Faculty of Medicine, Kyoto University, Japan.
Taniguchi
T
T
Kameyama
M
M
Fujiwara
M
M
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002531:Cerebellum / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism; D003342:Corpus Striatum / Q000378:metabolism; D005445:Flunitrazepam / Q000378:metabolism*; D005968:Glutamate Decarboxylase / Q000378:metabolism*; D006624:Hippocampus / Q000378:metabolism; D002534:Hypoxia, Brain / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D009118:Muscimol / Q000378:metabolism*; D017830:Octoxynol; D011092:Polyethylene Glycols / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011963:Receptors, GABA-A / Q000378:metabolism*
D011963:Receptors, GABA-A; D009118:Muscimol; D011092:Polyethylene Glycols; D005445:Flunitrazepam; D017830:Octoxynol; D005968:Glutamate Decarboxylase