EFFECTS OF GABA ANALOGS OF RESTRICTED CONFORMATION ON GABA TRANSPORT IN ASTROCYTES AND BRAIN CORTEX SLICES AND ON GABA RECEPTOR-BINDING

—The effects of a variety of acyclic or heterocyclic GABA analogues on GABA receptor binding and on high affinity transport of GABA in cultured astrocytes and mini‐slices of brain cortex were studied. The receptor and transport sites were found to be stereospecific and they exhibited opposite stereoselectivity for (R)‐ and (S)‐trans‐4‐amino‐4‐methylcrotonic acid and (R)‐ and (S)‐β‐proline. The most potent inhibitors of GABA binding were (RS)‐4, 5‐dihydromuscimol, muscimol, GABA, isoguvacine and isonipecotic acid with IC50values of, respectively, 0.009, 0.006, 0.033, 0.037 and 0.33 μM. Under the present experimental conditions the following compounds inhibited preferentially the glial transport system: (3RS, 4SR)‐4‐hydroxynipecotic acid, guvacine, (RS)‐N‐methylnipecotic acid, (RS)‐β‐proline and β‐alanine (IC50 values 10, 25, 70, 320 and 1000 μM, respectively vs. 200, 100, 300, 1200 and >5000 for neuronal transport). On the other hand, (R)‐trans‐4‐amino‐4‐methylcrotonic acid, (3RS, 4SR, 5SR)‐4‐hydroxy‐5‐methymipecotic acid and (RS)‐3‐hydroxy‐5‐aminovaleric acid preferentially inhibited neuronal transport as studied in mini‐slices of brain cortex (IC50 values 160, 300 and 430 μM, respectively vs. 500, > 5000 and 1400 μM for glial transport). Copyright © 1979, Wiley Blackwell. All rights reserved