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

Abstract: High-affinity binding sites (apparent K _D= 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.