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Dual Action of Pentobarbitone on GABA Binding: Role of Binding Site Integrity
Author(s) -
Willow Max,
Johnston Graham A. R.
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.tb04680.x
Subject(s) - bicuculline , membrane , chemistry , binding site , biophysics , gabaa receptor , gaba receptor , homogenization (climate) , mechanism of action , receptor , pharmacology , biochemistry , in vitro , biology , biodiversity , ecology
— The effects of pentobarbitone on the binding of γ‐aminobutyric acid (GABA) to crude synaptosomal rat brain membranes were studied. In extensively washed P 2 membranes, pentobarbitone had a biphasic action: at concentrations ranging between 12.5 and 500 μ m , pentobarbitone enhanced GABA binding in a concentration‐dependent manner; at concentrations greater than 500 μ m , this enhancement was progressively reversed towards control levels of GABA binding. The effect of pentobarbitone seen at higher concentrations may reflect a GABA‐mimetic action, since similar concentrations enhanced diazepam binding to washed P 2 membranes, an effect antagonized by bicuculline methochloride and picrotoxinin. When washed P 2 membranes were incubated in 0.5% Triton X‐100 (30 min at 37°C), the enhancement of GABA binding by low concentrations of pentobarbitone was abolished, while at higher concentrations GABA binding was progressively inhibited, suggesting that the GABA‐mimetic action is retained. When washed P 2 membranes were subjected to high‐frequency homogenization, the biphasic dose‐response relationship for pentobarbitone was markedly shifted to the right. The choice of membrane preparation appears to be a critical factor in examining drug‐receptor interactions in vitro, at least for those involving GABA and the barbiturates.