High‐Affinity Binding of [3H]Desipramine to Rat Brain: A Presynaptic Marker for Noradrenergic Uptake Sites
High‐Affinity Binding of [3H]Desipramine to Rat Brain: A Presynaptic Marker for Noradrenergic Uptake Sites
复制标题
[3H]地昔帕明与大鼠大脑的高亲和力结合：去甲肾上腺素能摄取位点的突触前标记
作者：
M. Rehavi;P. Skolnick;M. Brownstein;S. Paul
摘要：[3H]地西帕明的高亲和力结合位点（表观KD= 1.5 nM）已经在大鼠脑膜中得到证实和表征。[3H]地西帕明的结合被发现是饱和的、可逆的、热敏的、钠依赖的，并且在大脑的各个区域具有区域性分布。在中隔、大脑皮层和下丘脑中发现了高浓度的[3H]地西帕胺结合位点，而在髓质、小脑和纹状体中发现了较低的浓度。在抑制高亲和力[3H]地西帕胺结合的一系列药物的效力与它们阻断去甲肾上腺素摄取到突触体的能力之间，观察到非常好的相关性（r= 0.81, P < 0.001）。在6 -羟多巴胺损伤大鼠中，[3H]去甲肾上腺素摄取和[3H]去西帕明结合明显减少，[3H]血清素摄取和[3H]丙咪嗪结合均无显著变化。这些结果表明，[3hj地西帕明]与[3H]丙咪嗪的高亲和力结合在药理学和生物化学上不同，[3H]地西帕明的高亲和力结合位点与去甲肾上腺素的摄取位点之间存在密切关系。
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.