Basile A S, Ostrowski N L, Skolnick P
J Pharmacol Exp Ther. 1987 Mar;240(3):1006-13.
A statistically significant decrease in the density of peripheral benzodiazepine receptors was observed in renal membranes of rats beginning 2 weeks after adrenalectomy when compared with sham-operated controls. This decrease in peripheral benzodiazepine receptor density was manifest as a decrease in the maximum binding of two ligands, [3H]Ro 5-4864 and [3H]PK 11195, without accompanying changes in their Kd for this site. Similar changes were not seen in another aldosterone-sensitive organ, the submandibular salivary gland. The decrease in peripheral benzodiazepine receptor density observed in adrenalectomized rat renal membranes was restored to control levels after 1 week of aldosterone administration using a dose (12.5 micrograms/kg/day) that had no effect on peripheral benzodiazepine receptor density in sham-operated animals. In contrast, dexamethasone administration (50 micrograms/kg/day, 1 week) had no effect on renal peripheral benzodiazepine receptor density when administered to either adrenalectomized or sham-operated rats. Further, adrenal demedullation had no effect on renal peripheral benzodiazepine receptor density or affinity. The decrease in peripheral benzodiazepine receptor density was localized to the renal cortex and the outer stripe of the medulla by gross dissection of renal slices and renal tissue section autoradiography. The specific effect of adrenalectomy on renal peripheral benzodiazepine receptor density, the lack of direct effect of aldosterone on [3H] Ro 5-4864 binding and the localization of the change in peripheral benzodiazepine receptor density to the renal cortex and outer stripe suggest that these changes may reflect an adaptation of the renal nephron (possibly the distal convoluted tubule, intermediate tubule and/or the collecting duct) to the loss of mineralocorticoid hormones.
与假手术对照组相比,在肾上腺切除术后2周开始,观察到大鼠肾膜中外周苯二氮䓬受体密度有统计学意义的下降。外周苯二氮䓬受体密度的这种下降表现为两种配体[3H]Ro 5-4864和[3H]PK 11195的最大结合量减少,而它们对此位点的解离常数(Kd)没有伴随变化。在另一个醛固酮敏感器官下颌下唾液腺中未观察到类似变化。使用对假手术动物外周苯二氮䓬受体密度无影响的剂量(12.5微克/千克/天)给予醛固酮1周后,肾上腺切除大鼠肾膜中外周苯二氮䓬受体密度的下降恢复到对照水平。相比之下,给予地塞米松(50微克/千克/天,1周)对肾上腺切除或假手术大鼠的肾外周苯二氮䓬受体密度均无影响。此外,肾上腺去髓质对肾外周苯二氮䓬受体密度或亲和力没有影响。通过对肾切片进行大体解剖和肾组织切片放射自显影,发现外周苯二氮䓬受体密度的下降定位于肾皮质和髓质外带。肾上腺切除术对肾外周苯二氮䓬受体密度的特定影响、醛固酮对[3H]Ro 5-4864结合的直接影响的缺乏以及外周苯二氮䓬受体密度变化定位于肾皮质和外带表明,这些变化可能反映了肾单位(可能是远曲小管、中间小管和/或集合管)对盐皮质激素丧失的适应。