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

The binding of the GABA agonist [3H]THIP to rat brain synaptic membranes.

THIP (4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol) is a specific GABA agonist with potent analgesic properties. The binding of radioactive THIP to thoroughly washed, frozen, and thawed membranes isolated from rat brains has been studied at 2 degrees C under sodium ion-free conditions and compared with the binding of [3H]GABA and [3H]piperidine-4-sulphonic acid ([3H]P4S). The best computer fits to the experimental data were in all cases attained with a receptor model based on three independent binding sites, of which only the high- and medium-affinity sites could be characterised satisfactorily. While the KD values were found to be comparable for all three ligands employed, the density of the high-affinity binding site ( BM1) was, with the exception of the membranes from the cerebellum, considerably lower for [3H]THIP than for [3H]GABA and [3H]P4S. The regional distribution of the GABA receptors, which bind [3H]THIP, was different from those recognizing [3H]GABA and [3H]P4S. A number of analogues, including asymmetric compounds with known configuration, were tested as inhibitors of the binding of [3H]GABA, [3H]muscimol, [3H]THIP, [3H]isoguvacine, and [3H]P4S. The concentrations of the asymmetric compounds required for the inhibition of [3H]P4S binding were much higher than those required for the displacement of [3H]GABA, [3H]muscimol, [3H]THIP, and [3H]isoguvacine. The comparable relative potencies of inhibitors do, however, indicate that all of the ligands bind to the GABA receptors.[1]


  1. The binding of the GABA agonist [3H]THIP to rat brain synaptic membranes. Falch, E., Krogsgaard-Larsen, P. J. Neurochem. (1982) [Pubmed]
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