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Interactions of Salsolinol and β‐Carbolines with Cerebral GABA/Benzodiazepine Receptor Complex: Alteration during Alcohol Dependence
Author(s) -
Kuriyama Kinya,
Taguchi Junichi,
Hashimoto Tsuneichi
Publication year - 1988
Publication title -
australian drug and alcohol review
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.018
H-Index - 74
eISSN - 1465-3362
pISSN - 0819-5331
DOI - 10.1080/09595238880000111
Subject(s) - flunitrazepam , chemistry , muscimol , gabaa receptor , gaba receptor , chloride channel , benzodiazepine , receptor , biochemistry
Effects of salsolinol and 3‐carboxy ester of β‐carboline, which are known as condensation products of acetaldehyde formed in mammalian brain, on γ‐amino‐butyric acid (GABA) A receptor/benzodiazepine receptor/chloride channel complex and its alterations during the development of alcohol dependence were studied. In synaptic membrane preparation, ethyl β‐carboline‐3‐carboxylate (β‐ECC) was found to bind to a different site from that for benzodiazepines. The benzodiazepine‐stimulated [ 3 H] muscimol binding to GABA A receptor was suppressed by β‐ECC, whereas [ 3 H]β‐ECC binding was found to be suppressed by GABA, muscimol and secobarbital. Gel column chromatography using Sephadex G‐200 of the solubilized fraction from cerebral particulate fraction by sodium deoxycholate indicated that [ 3 H]β‐ECC binding site was eluted in the same fraction (molecular weight = 230,000) as the binding sites for [ 3 H]muscimol, [ 3 H]flunitrazepam, and [ 3 H]t‐butylbicycloorthobenzoate, known as a blocker of chloride channel. Salsolinol stimulated the specific bindings of [ 3 H]flunitrazepam and [ 3 H]β‐ECC to cerebral synaptic membranes in the presence of chloride anion. GABA‐stimulated 36 C1‐influx into membrane vesicles was stimulated by flunitrazepam, while attenuated by β‐ECC, and these effects of flunitrazepam and β‐ECC were accentuated by salsolinol. In alcohol dependent mice, the stimulating effect of salsolinol on the bindings of [ 3 H]flunitrazepam and [ 3 H]β‐ECC to cerebral synaptic membrane was eliminated. These results indicate that β‐ECC binding site may reside on GABA A receptor complex, and salsolinol may modulate the functions of benzodiazepine and β‐ECC binding sites in the brain. The present results also suggest that the alteration of modulatory action of salsolinol on the cerebral [ 3 H]flunitrazepam and [ 3 H]β‐ECC binding sites may be involved in the occurrence and/or maintenance of alcohol dependent conditions.