High‐Affinity Binding of [3H]Desipramine to Rat Brain: A Presynaptic Marker for Noradrenergic Uptake Sites

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Abstract
High-affinity binding sites (apparent KD= 1.5 nM) for [3H]desipramine have been demonstrated and characterized in membranes prepared from rat brain. The binding of [3H]desipramine was found to be saturable, reversible, heat-sensitive, sodium-dependent, and regionally distributed among various regions of the brain. High concentrations of [3H]desipramine binding sites were found in the septum, cerebral cortex, and hypothalamus, whereas lower concentrations were found in the medulla, cerebellum, and corpus striatum. A very good correlation (r= 0.81, P < 0.001) was observed between the potencies of a series of drugs in inhibiting high-affinity [3H]desipramine binding and their capacity to block norepinephrine uptake into synaptosomes. In 6-hydroxydopamine-lesioned rats there was a marked decrease in [3H]norepinephrine uptake and [3H]desipramine binding with no significant alterations in either [3H]serotonin uptake or [3H]imipramine binding. These results suggest that the high-affinity binding of [3HJdesipramine to rat brain membranes is pharmacologically and biochemically distinct from the high-affinity binding of [3H]imipramine, and that there is a close relationship between the high-affinity binding site for [3H]desipramine and the uptake site for norepinephrine.