High affinity renal [3H]flunitrazepam binding: Characterization,localization, and alteration in hypertension |
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Authors: | John W Regan Henry I Yamamura Shizuo Yamada William R Roeske |
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Institution: | Departments of Pharmacology, Psychiatry and Internal Medicine, The University of Arizona, Health Sciences Center, Tucson, Arizona 85724, USA |
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Abstract: | The binding of 3H]flunitrazepam was studied in membranes prepared from the kidney and cerebral cortex of unilaterally nephrectomized rats made hypertensive by simultaneous deoxycorticosterone acetate (DOCA) and NaCl administration. A significant 35–43% increase in the number of 3H]flunitrazepam binding sites (Bmax) was found in the renal membranes prepared from the hypertensive rats; there was no change in the density of binding sites in the membranes obtained from the cerebral cortex. The Kd of 3H]flunitrazepam binding did not change either in the renal or in the cerebral membranes (~ 12 nM in the kidney and ~2.0 nM in the brain). Drug specificity studies with renal membranes showed that the inhibition of 3H]flunitrazepam binding by various benzodiazepines did not jibe with their pharmacologic potency as anxiolytic agents. An intrarenal distribution of specific 3H]flunitrazepam binding was found in the bovine kidney; specific binding was greatest in the outer cortex and virtually absent in the medulla, the minor calyx and the renal artery. The evidence that the renal benzodiazepine binding site is of high affinity, is specific, has a unique distribution, and is regulated during hypertension suggests that it may be associated with an important pathophysiologic structure. |
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Keywords: | To whom reprint request should be addressed |
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