High-affinity binding of [3H]desipramine to rat brain: a presynaptic marker for noradrenergic uptake sites.

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 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.

journal_name

J Neurochem

authors

Rehavi M,Skolnick P,Brownstein MJ,Paul SM

doi

10.1111/j.1471-4159.1982.tb05326.x

subject

Has Abstract

pub_date

1982-04-01 00:00:00

pages

889-95

issue

4

eissn

0022-3042

issn

1471-4159

journal_volume

38

pub_type

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