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Competitive Inhibition of γ‐Aminobutyric Acid Receptor Binding by N ‐2‐Hydroxyethylpiperazine‐N′‐2‐ Ethanesulfonic Acid and Related Buffers
Author(s) -
Tunnicliff Godfrey,
Smith Julie A.
Publication year - 1981
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.1471-4159.1981.tb01708.x
Subject(s) - muscimol , hepes , chemistry , binding site , receptor , membrane , gabaa receptor , biophysics , synaptic membrane , biochemistry , stereochemistry , biology
Several Good buffers (MOPS, ACES, BES, HEPES, ADA, and PIPES) competitively inhibited both high‐affinity and low‐affinity [ 3 H]γ‐aminobutyric acid receptor binding to rat brain synaptic membranes. The most potent inhibitor was MOPS, which had K i values of 180 nM and 79 nM for the high‐ and low‐affinity binding sites, respectively. HEPES had K i , values of 2.25 MM and 115 μM. The buffers had no appreciable effect on sodium‐dependent GABA binding or on γ‐aminobutyrate aminotransferase activity. Surprisingly, the buffers were extremely ineffectual as inhibitors of either high‐ or low‐affinity [ 3 H]muscimol binding. Indeed, they were of the order of 10 5 times less effective in this case than against [ 3 h]GABA binding. These results clearly show (a) that the use of such buffers as MOPS or HEPES should be avoided in studying the interaction of GABA with its receptor, and (b) the binding sites of [ 3 H]GABA and [ 3 H]muscimol are not identical.