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Kinetic Modulation by GABAergic Agents of High‐ and Low‐Affinity Binding of [ 3 H]Methyl β‐Carboline‐3‐Carboxylate
Author(s) -
Maksay Gabor,
Simonyi Miklós
Publication year - 1988
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.1471-4159.1988.tb02489.x
Subject(s) - picrotoxin , dissociation (chemistry) , chemistry , kinetics , dissociation constant , stereochemistry , gabaergic , antagonist , medicinal chemistry , biophysics , receptor , biochemistry , biology , physics , quantum mechanics
The kinetics of dissociation of [ 3 H]methyl β‐carboline‐3‐carboxylate (β‐CCM) binding was studied in a synaptosomal membrane preparation of rat cerebral cortex. Dissociation was biphasic: a faster phase (10–30% contribution) was followed by a slower phase. Picrotoxin pre‐treatment at 22°C enhanced the equilibrium binding of [ 3 H]β‐CCM. The half‐life of the slower phase of β‐CCM dissociation (t II 1/2 ) was increased by 60 μ M picrotoxin from 1.7 min to 3.3 min. The dissociation of [ 3 H]β‐CCM was identical when initiated by an excess of either diazepam or β‐CCM. Quasi‐equilibrium Scatchard analysis of [ 3 H]β‐CCM binding was performed by a kinetic separation of the rapid and slow phases of dissociation. The slow and rapid phases represented β‐CCM binding sites of high and low affinity, respectively. The dissociation of [ 3 H]β‐CCM (control t II 1/2 = 2.0 min) was decelerated by the γ‐aminobutyric acid (GABA) antagonist 3–α‐hydroxy‐16‐imino‐5β‐17‐azaandrostan‐11‐one (R 5135) (t II 1/2 = 2.5 min) and accelerated by GABA (t II 1/2 = 1.6 min). GABA inhibited both high‐ and low‐affinity β‐CCM bindings.