[Mitochondrial benzodiazepine receptors (MBR) in association with neurological disorders].

Abstract

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.

• Authors: M Yoshii, Y Nakamoto, S Watabe, G Mugishima, H Habu, T Shiotani, T Nabeshima
• Journal: Nihon shinkei seishin yakurigaku zasshi = Japanese journal of psychopharmacology (Nihon Shinkei Seishin Yakurigaku Zasshi) Vol. 18 Issue 2 Pg. 49-54 (Apr 1998) ISSN: 1340-2544 [Print] Japan
• PMID: 9656233 (Publication Type: Journal Article, Review)

Chemical References

• Benzodiazepinones
• Convulsants
• Receptors, GABA-A
• 4'-chlorodiazepam

Topics

• Animals
• Benzodiazepinones
• Convulsants
• Mice
• Mice, Mutant Strains
• Mitochondria (physiology)
• Receptors, GABA-A (physiology)
• Seizures (chemically induced, metabolism)