Modulation of diazepam-insensitive GABA_A receptors by micromolar concentrations of thyroxine and related compounds in vitro

详细信息    查看全文

• 作者：Hitoshi Ishibashi^a ; ^{isibasi@nips.ac.jp} ; Michael-Robin Witt^b ; Junichi Nabekura^a ; Mogens Nielsen^c
• 关键词：3 ; 5-T2 ; 3&prime ; 5&prime ; -diiodothyronine ; rT3 ; reverse T3 ; TETRAC ; 3 ; 5 ; 3&prime ; 5&prime ; -tetraiodothyroacetic acid ; T3 ; triiodothyronine ; THIP ; Gaboxadol or 4 ; 5 ; 6 ; 7 ; -tetrahydroisoxazolo(5 ; 4-c)pyridine-3ol
• 刊名：Brain Research
• 出版年：2013
• 出版时间：15 January, 2013
• 年：2013
• 卷：1490
• 期：Complete
• 页码：1-8
• 全文大小：787 K

文摘

The effects of thyroxine and its related compounds on the benzodiazepine-insensitive ¦Ã-aminobutyric acid type A (GABA_A) receptors were studied. Thyroxine at micromolar concentrations potentiated the ³H-Ro15-4513 binding to rat brain membranes in-vitro in the thalamus, striatum, cortex and hippocampus, but not in cerebellum. In the thalamus, the rank order of potency was the following: 3,3¡ä,5,5¡ä-tetraiodothyroacetic acid (TETRAC)>L-thyroxine>3,5-diiodo-l-thyronine (3,5-T2). TETRAC induced a slight potentiation of flumazenil binding to diazepam-sensitive GABA_A receptors in the thalamus and striatum while no effect was found in cortex and hippocampus. Consequently, we examined whether these compounds could exert their modulatory effect on the currents mediated by benzodiazepine-insensitive GABA_A receptors. The diazepam-insensitive GABA_A receptor-mediated currents were recorded from acutely isolated rat ventrobasal thalamic neurons by applying low concentrations of 4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol (THIP). TETRAC and thyroxine at low ¦ÌM concentrations potentiated the THIP-evoked currents, although 3,5-T2 had no effect on the THIP-induced currents. Ethanol had no effect on the enhancing effects of TETRAC. TETRAC itself evoked GABA_A receptor-mediated currents at high concentrations beyond 30 ¦ÌM. Although the effects of TETRAC and thyroxine were observed at non-physiological concentrations of hormones, the present results might lead to new lead structures with specificity to diazepam-insensitive GABA_A receptor subtypes.