Preservation of peripheral benzodiazepine receptors: differential effects of freezing on (/sup 3/H)Ro 5-4864 and (3H)PK 11195 binding
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 Bmax of two ligands (/sup 3/H)Ro 5-4864 and (/sup 3/H)PK 11195, without accompanying changes in their apparent affinity (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 in 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 (/sup 3/H)Ro 5-4864 binding, and the localization of the change in peripheral benzodiazepine receptor density to the renal cortex and outer stripe suggests 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.
- Research Organization:
- NIADDK, Bethesda, MD
- OSTI ID:
- 6332534
- Journal Information:
- J. Pharmacol. Methods; (United States), Vol. 2
- Country of Publication:
- United States
- Language:
- English
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63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
RECEPTORS
BIOCHEMICAL REACTION KINETICS
TEMPERATURE EFFECTS
TRANQUILIZERS
ADRENALECTOMY
AFFINITY
ALDOSTERONE
AUTORADIOGRAPHY
CELL MEMBRANES
DEXAMETHASONE
FREEZING
IN VITRO
KIDNEYS
LIGANDS
RATS
TRITIUM COMPOUNDS
ADRENAL HORMONES
ALDEHYDES
ANIMALS
BODY
CELL CONSTITUENTS
CENTRAL NERVOUS SYSTEM AGENTS
CORTICOSTEROIDS
DRUGS
GLUCOCORTICOIDS
HORMONES
HYDROXY COMPOUNDS
KETONES
KINETICS
LABELLED COMPOUNDS
MAMMALS
MEDICINE
MEMBRANE PROTEINS
MEMBRANES
MINERALOCORTICOIDS
ORGANIC COMPOUNDS
ORGANS
PREGNANES
PROTEINS
PSYCHOTROPIC DRUGS
REACTION KINETICS
RODENTS
STEROID HORMONES
STEROIDS
SURGERY
VERTEBRATES
550201* - Biochemistry- Tracer Techniques
560200 - Thermal Effects