Effects of guanyl nucleotides on [3H]flunitrazepam binding to rat hippocampal synaptic membranes: equilibrium binding and dissociation kinetics.
The effects of guanyl nucleotides on the binding of [3H]flunitrazepam to rat hippocampal synaptic membranes were studied. In equilibrium binding studies, gamma-amino-n-butyric acid (GABA) increased and GTP decreased the binding affinity of [3H]flunitrazepam; GTP also caused a decrease in binding capacity. The effect, however, is variable. In studies of the dissociation kinetics of [3H]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 mimicked 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 [3H]flunitrazepam. The nature of the benzodiazepine receptor, its actions, and the possible role of cyclic AMP as a second messenger are discussed.
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D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D001570:Benzodiazepinones / Q000378:metabolism; D003975:Diazepam / Q000378:metabolism; D005442:Flumazenil; D005445:Flunitrazepam / Q000378:metabolism*; D006150:Guanine Nucleotides / Q000494:pharmacology*; D006160:Guanosine Triphosphate / Q000494:pharmacology; D006165:Guanylyl Imidodiphosphate / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D011963:Receptors, GABA-A / Q000378:metabolism; D013570:Synaptic Membranes / Q000187:drug effects / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
D001570:Benzodiazepinones; D006150:Guanine Nucleotides; D011963:Receptors, GABA-A; D006165:Guanylyl Imidodiphosphate; D005442:Flumazenil; D005680:gamma-Aminobutyric Acid; D005445:Flunitrazepam; D006160:Guanosine Triphosphate; D000255:Adenosine Triphosphate; D003975:Diazepam