High-affinity binding of [3H]desipramine to rat brain: a presynaptic marker for noradrenergic uptake sites.
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 less than 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 [3H]desipramine 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.
D000818:Animals; D001665:Binding Sites; D001667:Binding, Competitive; D001692:Biological Transport; D001921:Brain / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D003891:Desipramine / Q000378:metabolism*; D006892:Hydroxydopamines / Q000494:pharmacology; D007099:Imipramine / Q000378:metabolism; D007700:Kinetics; D008297:Male; D009638:Norepinephrine / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000378:metabolism; D014018:Tissue Distribution
D006892:Hydroxydopamines; D012701:Serotonin; D007099:Imipramine; D003891:Desipramine; D009638:Norepinephrine