Delbende C, Jégou S, Tranchand-Bunel D, Blasquez C, Vaudry H
UA CNRS 650, Unité Affiliée à l'INSERM, Université de Rouen, Mont-Saint-Aignan, France.
Brain Res. 1989 Sep 11;497(1):86-93. doi: 10.1016/0006-8993(89)90973-6.
The effect of gamma-aminobutyric acid (GABA) on release of alpha-melanocyte-stimulating hormone (alpha-MSH) from hypothalamic neurons was investigated in vitro using the perifusion technique. Rat hypothalamic slices were continuously superfused with Krebs-Ringer medium and the release of alpha-MSH in the effluent perifusate was monitored by means of a sensitive and specific radioimmunoassay method. Infusion of 50 mM K+ for 15 min induced a transient increase of alpha-MSH release (5- to 8-fold above the spontaneous level). Infusion of the same dose of K+ for 75 min caused a brief discharge of alpha-MSH during the first 30 min followed by sustained release of the neuropeptide. The effect of GABA was investigated 27 min after the onset of KCl infusion. Application of GABA (5 x 10(-5) M) resulted in a significant and reversible inhibition of K+-induced alpha-MSH release. The GABAA agonist, muscimol (10(-4) M), produced a prolonged inhibition of K+-evoked alpha-MSH release, while the GABAB agonist, baclofen (10(-4) M), was devoid of effect on hypothalamic alpha-MSH release. Bicuculline (10(-4) M), a specific GABAA antagonist, had no effect when added alone to the medium but totally reversed the inhibitory effect of GABA on K+-induced alpha-MSH release. Taken together, these data suggest that exogenous GABA exerts an inhibitory control on alpha-MSH neurons. Our data also show that the effect of GABA on alpha-MSH release by hypothalamic neurons is mediated through GABAA-type receptors.(ABSTRACT TRUNCATED AT 250 WORDS)
采用灌流技术在体外研究了γ-氨基丁酸（GABA）对下丘脑神经元释放α-黑素细胞刺激素（α-MSH）的影响。用Krebs-Ringer培养基持续灌流大鼠下丘脑切片，通过灵敏且特异的放射免疫分析法监测流出灌流液中α-MSH的释放。输注50 mM K⁺ 15分钟可诱导α-MSH释放短暂增加（比自发水平高5至8倍）。输注相同剂量的K⁺ 75分钟，在前30分钟内导致α-MSH短暂释放，随后该神经肽持续释放。在输注KCl开始27分钟后研究GABA的作用。应用GABA（5×10⁻⁵ M）可导致K⁺诱导的α-MSH释放受到显著且可逆的抑制。GABAA激动剂蝇蕈醇（10⁻⁴ M）可延长对K⁺诱发的α-MSH释放的抑制作用，而GABAB激动剂巴氯芬（10⁻⁴ M）对下丘脑α-MSH释放无影响。特异性GABAA拮抗剂荷包牡丹碱（10⁻⁴ M）单独添加到培养基中时无作用，但完全逆转了GABA对K⁺诱导的α-MSH释放的抑制作用。综上所述，这些数据表明外源性GABA对α-MSH神经元发挥抑制性调控作用。我们的数据还表明，GABA对下丘脑神经元释放α-MSH的作用是通过GABAA型受体介导的。（摘要截短至250字）
