Modulation of [3H] TBOB binding to the rodent GABAA receptor by simple disaccharides

被引:4
|
作者
Rezai, N [1 ]
Duggan, C [1 ]
Cairns, D [1 ]
Lees, G [1 ]
Chazot, PL [1 ]
机构
[1] Univ Sunderland, Inst Pharm Chem & Biomed Sci, Sch Hlth Nat & Social Sci, Sunderland SR1 3SD, Tyne & Wear, England
关键词
GABA(A) receptor; lactose [H-3] TBOB; forebrain; cerebellum; beta-linked sugars;
D O I
10.1016/S0006-2952(02)01611-8
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
We have recently reported evidence that a simple beta-linked alkylated mannose reversibly increased the magnitude of GABA(A) receptor currents evoked in cultured rat pyramidal neurons whilst concomitantly reducing the incidence of spontaneous synaptic activity. In this present study, the effects of the simple beta-linked disaccharide, lactose was investigated using a [H-3] TBOB (t-[H-3] butylbicycloorthobenzoate) binding assay in adult rat forebrain and cerebellum membranes. Lactose elicited a significant potentiation of [H-3] TBOB binding to well-washed forebrain and cerebellar membranes (mean E-max values = 367 and 287%; mean EC50 values = 1.5 and 30 muM, respectively, N = 4). The alpha-linked disaccharides, maltose and sucrose also potentiated [H-3] TBOB binding, but with 100-600-fold higher EC50 values than lactose. The lactose-mediated potentiation of [H-3] TBOB in the forebrain and cerebellum was completely abolished in the presence of 0.3 muM GABA. Over the concentration range in which significant potentiation of [H-3] TBOB binding was detected, lactose elicited no significant effect upon [H-3] flunitrazepam binding. This study demonstrated that lactose can modulate the GABA(A) receptor channel. allosterically coupled to the agonist site, but independent of the benzodiazepine site. Furthermore, lactose displayed differential effects upon forebrain and cerebellar GABA(A) receptors indicating that it may be a novel subtype selective agent. (C) 2002 Elsevier Science Inc. All rights reserved.
引用
收藏
页码:619 / 623
页数:5
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