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Effects of Guanyl Nucleotides on [ 3 H]Flunitrazepam Binding to Rat Hippocampal Synaptic Membranes: Equilibrium Binding and Dissociation Kinetics
Author(s) -
Fung S.C.,
Fillenz M.
Publication year - 1985
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.1471-4159.1985.tb07135.x
Subject(s) - chemistry , flunitrazepam , gtp' , dissociation constant , dissociation (chemistry) , kinetics , binding site , flumazenil , stereochemistry , biophysics , nucleotide , antagonist , gabaa receptor , biochemistry , receptor , enzyme , biology , physics , quantum mechanics , gene
The effects of guanyl nucleotides on the binding of [ 3 H]flunitrazepam to rat hippocampal synaptic membranes were studied. In equilibrium binding studies, γ‐amino‐ n ‐butyric acid (GABA) increased and GTP decreased the binding affinity of [ 3 H]flunitrazepam; GTP also caused a decrease in binding capacity. The effect, however, is variable. In studies of the dissociation kinetics of [ 3 H]flunitrazepam using diazepam and the antagonist Ro 15–1788 as the displacers, there was evidence of two dissociation rate constants. GTP increased both the fast and slow‐dissociation rate constants and increased the ratio of the slow‐dissociation binding state. The effect of GTP was mimickled by its nonhydrolyzable analogue 5′‐guanylylimidodiphosphate but not by ATP and occurred when diazepam, but not when Ro 15–1788, was used as the displacer. GABA antagonized the effect of GTP on the dissociation of [ 3 H]flunitrazepam. The nature of the benzodiazepine recepter, its actions, and the possible role of cyclic AMP as a second messenger are discussed.