TY - JOUR
T1 - High‐Affinity Binding of [3H]Desipramine to Rat Brain
T2 - A Presynaptic Marker for Noradrenergic Uptake Sites
AU - Rehavi, M.
AU - Skolnick, P.
AU - Brownstein, M. J.
AU - Paul, S. M.
PY - 1982/4
Y1 - 1982/4
N2 - 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.
AB - 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.
KW - Norepinephrine uptake
KW - Serotonin uptake
KW - Tricyclic antidepressants
KW - [H]Desipramine binding
KW - [H]imipramine binding
UR - http://www.scopus.com/inward/record.url?scp=0020079977&partnerID=8YFLogxK
U2 - 10.1111/j.1471-4159.1982.tb05326.x
DO - 10.1111/j.1471-4159.1982.tb05326.x
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AN - SCOPUS:0020079977
SN - 0022-3042
VL - 38
SP - 889
EP - 895
JO - Journal of Neurochemistry
JF - Journal of Neurochemistry
IS - 4
ER -