Aldosterone-reversible decrease in the density of renal peripheral benzodiazepine receptors in the rat after adrenalectomy

AS Basile, NL Ostrowski and P Skolnick

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.

Volume 240, Issue 3, pp. 1006-1013, 03/01/1987
Copyright © 1987 by American Society for Pharmacology and Experimental Therapeutics

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