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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Kinetics of [3H]Ro 15-1788 binding to membrane-bound rat brain benzodiazepine receptors.

Ro 15-1788 is thought to interact specifically with the benzodiazepine receptor population in the mammalian CNS as an antagonist. We have compared the kinetics of interaction of this ligand with the benzodiazepine agonist flunitrazepam in the rat cerebellum. The association of [3H]Ro 15-1788 with the benzodiazepine receptor in this brain region is monoexponential, and the dissociation, initiated either by dilution or by displacement with a number of different ligands, also obeys simple monoexponential kinetics. There is no evidence of cooperative interactions with this ligand, and its dissociation is unaffected by the presence of 100 microM gamma-aminobutyric acid and/or 150 mM sodium chloride. In contrast, the dissociation of the agonist [3H]flunitrazepam is biphasic, and the possible interpretation of this data in terms of agonist-induced conformational change is discussed. Evidence is also presented that the mechanism of interaction of Ro 15-1788 with the benzodiazepine receptor population in hippocampal membranes is distinct from that found in the cerebellum.[1]


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