"Specific" Binding of [3H]Imipramine to Protease-Sensitive and Protease-Resistant Sites |
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Authors: | J Marcusson C J Fowler† H Hall† S B Ross† B Winblad‡ |
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Institution: | Department of Pathology, University of Umeå, Umeå, Sweden;Department of Geriatric Medicine, University of Umeå, Umeå, Sweden;Research and Development Laboratories, Astra Lükemedel AB, Södertälje, Sweden |
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Abstract: | A number of 5-hydroxytryptamine (5-HT) uptake inhibitors have been shown to displace the binding of 3H]imipramine to rat cortical membranes in a complex manner with Hill slopes less than unity. Norzimeldine displaced the binding of 3H]imipramine in a biphasic manner with IC50 values for the two components of about 30 nM and 30 microM. This latter site alone was found in tissues that had been treated with a protease. Binding to both of these sites was displaced by 10 microM desipramine. The protease-sensitive 3H]imipramine binding sites were found to be saturable, high-affinity binding sites with a KD of 8 nM. The number of these sites varied between brain regions and was positively correlated with the regional distribution of 14C]5-HT but not 3H]noradrenaline uptake. This was not the case however for the protease-resistant but desipramine-displaceable binding sites. Since most previous 3H]imipramine binding studies have been performed with high concentrations of desipramine (10 microM) to define "specific binding," these data would suggest that either protease-sensitivity or displacability by 1 microM norzimeldine would give more reliable estimates of the specific binding. |
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Keywords: | [3H]Imipramine binding 5-Hydroxytryptamine uptake Protease Norzimeldine Desipramine |
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