[Mitochondrial benzodiazepine receptors (MBR) in association with neurological disorders].
Ro 5-4864, a specific agonist of the peripheral-type benzodiazepine receptor (PBR), elicited convulsions 2.6 times more potently in EL mice (an animal model of epilepsy) than in DDY mice (control animal). A binding assay revealed a 50% higher density of [3H] Ro 5-4864 binding sites in the mitochondrial fraction (i.e., mitochondrial benzodiazepine receptors; MBR) of the brain tissues in EL mice as compared with DDY mice. On an elevated plus-maze, EL mice showed fear responses similar to those increased in DDY mice after PBR stimulation, suggesting a hyperfunction of MBR underlying the abnormal behaviors of EL mice. In fluorometric studies using NG108-15 cells, Ro 5-4864 depolarized mitochondrial membranes and, possibly as a consequence of this, raised intracellular Ca2+. Finally, we propose that MBR could be a major target of therapy for various neurological disorders, so drugs such as "mitochondrial membrane stabilizers" should be developed.
Yoshii
M
M
Department of Neurophysiology, Tokyo Institute of Psychiatry, Japan.
Nakamoto
Y
Y
Watabe
S
S
Mugishima
G
G
Habu
H
H
Shiotani
T
T
Nabeshima
T
T
D000818:Animals; D001570:Benzodiazepinones; D003292:Convulsants; D051379:Mice; D008817:Mice, Mutant Strains; D008928:Mitochondria / Q000502:physiology*; D011963:Receptors, GABA-A / Q000502:physiology*; D012640:Seizures / Q000139:chemically induced / Q000378:metabolism*
D001570:Benzodiazepinones; D003292:Convulsants; D011963:Receptors, GABA-A; C028513:4'-chlorodiazepam