Krause D N, Ikeda K, Roberts E
Brain Res. 1981 Nov 30;225(2):319-32. doi: 10.1016/0006-8993(81)90839-8.
The interaction of GABA (gamma-aminobutyric acid) and structurally-related compounds with postsynaptic GABA receptors was studied quantitatively by measuring receptor-mediated increases in membrane input conductance in isolated crayfish stretch receptor neurons (SRN). The following compounds, in order of decreasing potency, were effective agonists: muscimol greater than GABA greater than isoguvacine greater than (-)gamma-amino-beta-hydroxybutyric acid greater than beta-gu anidinopropionic acid greater than 3-aminopropanesulfonic acid greater than (+)gamma-amino-beta-hydroxybutyric acid greater than isonipecotic acid greater than THIP. A highly significant correlation was found between the log potencies for GABA agonists that were obtained in the SRN and those obtained in our laboratory using mammalian GABA receptor binding assays. Hill plot analyses of the log concentration-conductance data from the SRN indicated a Hill slope (nH) of approximately 2 for all agonists except GABA and guanidinopropionic acid (nH greater than 2), two compounds known to be actively accumulated by cellular GABA uptake processes. Nipecotic acid, guvacine, and L-alpha, beta-diaminopropionic acid, blockers of GABA uptake processes, had essentially no effect by themselves on the SRN membrane input conductance at concentrations up to 5 mM, however, they potentiated the effects of sub-maximal concentrations of GABA and decreased the steepness of the log concentration-conductance curve, and consequently nH, for GABA. The effects of muscimol, however, were not affected. When the influence of uptake processes was considered, it appeared that all agonists tested acted by the same cooperative mechanism which required at least two molecules of agonist to activate a receptor-ionophore unit.
通过测量分离的小龙虾伸展感受器神经元（SRN）中受体介导的膜输入电导增加，定量研究了γ-氨基丁酸（GABA）及结构相关化合物与突触后GABA受体的相互作用。以下化合物按效力递减顺序排列，均为有效激动剂：蝇蕈醇＞GABA＞异鹅膏蕈氨酸＞（-）γ-氨基-β-羟基丁酸＞β-胍基丙酸＞3-氨基丙烷磺酸＞（+）γ-氨基-β-羟基丁酸＞异哌啶酸＞四氢嘧啶。在SRN中获得的GABA激动剂的对数效力与在我们实验室使用哺乳动物GABA受体结合试验获得的对数效力之间发现了高度显著的相关性。对SRN中对数浓度-电导数据的希尔图分析表明，除GABA和胍基丙酸（nH＞2）外，所有激动剂的希尔斜率（nH）约为2，已知这两种化合物可通过细胞GABA摄取过程被主动积累。哌啶酸、鹅膏蕈氨酸和L-α，β-二氨基丙酸是GABA摄取过程的阻滞剂，在浓度高达5 mM时，它们自身对SRN膜输入电导基本没有影响，然而，它们增强了亚最大浓度GABA的作用，并降低了GABA对数浓度-电导曲线的陡度，从而降低了nH。然而，蝇蕈醇的作用不受影响。当考虑摄取过程的影响时，似乎所有测试的激动剂都通过相同的协同机制起作用，该机制至少需要两个激动剂分子来激活一个受体-离子载体单元。
