Barbaccia M L, Gandolfi O, Chuang D M, Costa E
Proc Natl Acad Sci U S A. 1983 Aug;80(16):5134-8. doi: 10.1073/pnas.80.16.5134.
Imipramine inhibits the serotonin uptake by binding with high affinity to regulatory sites of this uptake located on axons that release serotonin. The number of imipramine recognition sites located on crude synaptic membrane preparations is reduced by two daily injections of imipramine or desmethylimipramine for 3 weeks. When the binding sites for [3H]imipramine are down-regulated the Vmax of the neuronal uptake of serotonin is increased. Moreover, in minces prepared from the brain hippocampus of rats receiving imipramine in a dose regimen that reduces the number of [3H]imipramine recognition sites, the efficiency of imipramine as a blocker of the serotonin uptake is diminished. Hence the high-affinity binding sites for [3H]imipramine may have a physiological role in modulation of serotonin reuptake. Probably this is mediated by an endogenous effector of these regulatory sites. A nonpeptidic constituent of rat brain capable of displacing [3H]imipramine from its high-affinity binding site and of inhibiting the serotonin uptake in a dose-related manner has been extracted and its partial purification is described.
丙咪嗪通过与位于释放5-羟色胺的轴突上的这种摄取调节位点高亲和力结合来抑制5-羟色胺的摄取。通过每天两次注射丙咪嗪或去甲丙咪嗪，持续3周，可使粗制突触膜制剂上的丙咪嗪识别位点数量减少。当[3H]丙咪嗪的结合位点下调时，5-羟色胺的神经元摄取的Vmax增加。此外，在用能减少[3H]丙咪嗪识别位点数量的剂量方案接受丙咪嗪的大鼠脑海马制备的切碎组织中，丙咪嗪作为5-羟色胺摄取阻滞剂的效率降低。因此，[3H]丙咪嗪的高亲和力结合位点可能在调节5-羟色胺再摄取中具有生理作用。这可能是由这些调节位点的内源性效应物介导的。已从大鼠脑中提取出一种能够以剂量相关方式从其高亲和力结合位点置换[3H]丙咪嗪并抑制5-羟色胺摄取的非肽成分，并描述了其部分纯化过程。
