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“Specific” Binding of [ 3 H]Imipramine to Protease‐Sensitive and Protease‐Resistant Sites
Author(s) -
Marcusson J.,
Fowler C. J.,
Hall H.,
Ross S. B.,
Winblad B.
Publication year - 1985
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1985.tb12872.x
Subject(s) - desipramine , imipramine , binding site , protease , chemistry , biochemistry , biophysics , enzyme , stereochemistry , biology , endocrinology , medicine , hippocampus , alternative medicine , antidepressant , pathology
A number of 5‐hydroxytryptamine (5‐HT) uptake inhibitors have been shown to displace the binding of [ 3 H)imipramine to rat cortical membranes in a complex manner with Hill slopes less than unity. Norzimeldine displaced the binding of [ 3 H]imipramine in a biphasic manner with IC 50 values for the two components of about 30 n M and 30 μ M. This latter site alone was found in tissues that had been treated with a protease. Binding to both of these sites was displaced by 10μ M desipramine. The protease‐sensitive [ 3 H]imipramine binding sites were found to be saturable, high‐affinity binding sites with a K D of 8 n M . The number of these sites varied between brain regions and was positively correlated with the regional distribution of [ 14 C]5‐HT but not [ 3 H]noradrenaline uptake. This was not the case however for the protease resistant but desipramine‐displaceable binding sites. Since most previous [ 3 H]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 μ M norzimeldine would give more reliable estimates of the specific binding.