Li P P, Warsh J J, Sibony D, Chiu A
Section of Biochemical Psychiatry, Clarke Institute of Psychiatry, Toronto, Ontario, Canada.
Neurochem Res. 1988 Dec;13(12):1111-8. doi: 10.1007/BF00971627.
Chronic (21 days) treatment of rats with imipramine (10 mg/kg) did not change the density or affinity of alpha 1-adrenoceptors as measured by the specific binding of [3H]prazosin in rat cortical membranes, but produced the expected significant decrease in the density of beta-adrenoceptors labeled by [125I]iodocyanopindolol. The functional status of brain alpha 1-adrenoceptors was also assessed by measuring the noradrenaline (NA)-induced accumulation of [3H]inositol 1-phosphate (IP1) in brain slices from these animals. No apparent change was observed in the concentration-response relationship between NA and [3H]IP1 accumulation in rat cerebral cortex after chronic treatment with imipramine. At concentrations higher than 1 microM in vitro, imipramine and its metabolite, desipramine, produced a concentration-dependent decrease in the [3H]IP1 accumulation elicited by NA. This inhibitory effect is likely mediated by direct blockade of alpha 1-adrenoceptors by these drugs. As the endogenous drug concentration would not reach 1 microM in our preparation, the lack of changes in alpha 1-adrenoceptor response following chronic imipramine treatment are not likely attributable to residual imipramine or desipramine retained in the tissues. In conclusion, the above findings do not support previous suggestions that brain alpha 1-adrenoceptors are upregulated following chronic imipramine administration.
用丙咪嗪（10毫克/千克）对大鼠进行慢性（21天）治疗，并未改变大鼠皮质膜中通过[3H]哌唑嗪特异性结合所测定的α1 - 肾上腺素能受体的密度或亲和力，但却使由[125I]碘氰吲哚洛尔标记的β - 肾上腺素能受体密度出现预期的显著下降。还通过测量这些动物脑片中去甲肾上腺素（NA）诱导的[3H]肌醇1 - 磷酸（IP1）积累，来评估脑α1 - 肾上腺素能受体的功能状态。在用丙咪嗪进行慢性治疗后，大鼠大脑皮质中NA与[3H]IP1积累之间的浓度 - 反应关系未观察到明显变化。在体外浓度高于1微摩尔时，丙咪嗪及其代谢产物地昔帕明会使NA引发的[3H]IP1积累呈浓度依赖性下降。这种抑制作用可能是由这些药物直接阻断α1 - 肾上腺素能受体介导的。由于在我们的实验制剂中内源性药物浓度不会达到1微摩尔，慢性丙咪嗪治疗后α1 - 肾上腺素能受体反应缺乏变化不太可能归因于组织中残留的丙咪嗪或地昔帕明。总之，上述发现不支持先前关于慢性给予丙咪嗪后脑α1 - 肾上腺素能受体会上调的观点。
