Honegger U E, Disler B, Wiesmann U N
Biochem Pharmacol. 1986 Jun 1;35(11):1899-902. doi: 10.1016/0006-2952(86)90309-6.
The effects of the antidepressant drug desipramine (DMI) on the density of beta-adrenoceptor sites were studied on intact cultured human cells: skin fibroblasts, lung fibroblasts and macrophages. Direct binding studies were performed with the radioligand 3H-CGP 12177, a hydrophilic beta-adrenergic antagonist. The confluent cell cultures were exposed to DMI and all three cell types showed a dose-dependent decrease in the number of beta-adrenergic binding sites. This receptor desensitisation was only seen after chronic exposure of the cells to DMI. The extent of desensitisation was comparable to that seen in brain following chronic treatment of rats with DMI. The affinity of the binding sites to the radioligand was not affected by the antidepressant drug action. From these results we suggest that the in vivo effect of antidepressant drugs on postsynaptic beta-adrenoceptor density, at least in part, reflects a primary drug action and not only an adaptive change to presynaptic events.
在完整的培养人细胞（皮肤成纤维细胞、肺成纤维细胞和巨噬细胞）上研究了抗抑郁药去甲丙咪嗪（DMI）对β-肾上腺素能受体位点密度的影响。使用放射性配体³H-CGP 12177（一种亲水性β-肾上腺素能拮抗剂）进行直接结合研究。将汇合的细胞培养物暴露于DMI，所有三种细胞类型的β-肾上腺素能结合位点数量均呈剂量依赖性减少。这种受体脱敏仅在细胞长期暴露于DMI后才出现。脱敏程度与用DMI长期治疗大鼠后在脑中观察到的程度相当。结合位点对放射性配体的亲和力不受抗抑郁药作用的影响。从这些结果我们认为，抗抑郁药对突触后β-肾上腺素能受体密度的体内作用至少部分反映了药物的直接作用，而不仅仅是对突触前事件的适应性变化。
