Rehavi M, Skolnick P, Brownstein M J, Paul S M
J Neurochem. 1982 Apr;38(4):889-95. doi: 10.1111/j.1471-4159.1982.tb05326.x.
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.
已在大鼠脑制备的膜中证实并鉴定了[3H]去甲丙咪嗪的高亲和力结合位点（表观解离常数KD = 1.5 nM）。发现[3H]去甲丙咪嗪的结合具有饱和性、可逆性、热敏感性、钠依赖性，且在脑的不同区域呈区域分布。在隔区、大脑皮层和下丘脑发现了高浓度的[3H]去甲丙咪嗪结合位点，而在延髓、小脑和纹状体中浓度较低。观察到一系列药物抑制高亲和力[3H]去甲丙咪嗪结合的效力与其阻断去甲肾上腺素摄取到突触体中的能力之间具有非常好的相关性（r = 0.81，P < 0.001）。在6-羟基多巴胺损伤的大鼠中，[3H]去甲肾上腺素摄取和[3H]去甲丙咪嗪结合显著降低，而[3H]5-羟色胺摄取或[3H]丙咪嗪结合均无明显改变。这些结果表明，[3H]去甲丙咪嗪与大鼠脑膜的高亲和力结合在药理和生化上与[3H]丙咪嗪的高亲和力结合不同，并且[3H]去甲丙咪嗪的高亲和力结合位点与去甲肾上腺素摄取位点之间存在密切关系。
