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EFFECTS OF GABA ANALOGUES OF RESTRICTED CONFORMATION ON GABA TRANSPORT IN ASTROCYTES AND BRAIN CORTEX SLICES AND ON GABA RECEPTOR BINDING
Author(s) -
Schousboe A.,
Thorbek P.,
Hertz L.,
KrogsgaardLarsen P.
Publication year - 1979
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1979.tb11720.x
Subject(s) - muscimol , nipecotic acid , chemistry , stereochemistry , proline , amino acid , stereoselectivity , gamma aminobutyric acid , receptor , cortex (anatomy) , biochemistry , gabaa receptor , biology , neuroscience , neurotransmitter , catalysis
—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 IC 50 values 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 (IC 50 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 (IC 50 values 160, 300 and 430 μM, respectively vs. 500, > 5000 and 1400 μM for glial transport).