“Specific” Binding of [3H]Imipramine to Protease‐Sensitive and Protease‐Resistant Sites

Publisher Website
Google Scholar
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 μM. This latter site alone was found in tissues that had been treated with a protease. Binding to both of these sites was displaced by 10μM 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 μ. M) to define “specific binding,” these data would suggest that either protease‐sensitivity or displaceability by 1 μM norzimeldine would give more reliable estimates of the specific binding.