Furosemide inhibits 11 beta-hydroxysteroid dehydrogenase in vitro and in vivo
| Autor: | Brigitte M. Frey, Geneviève Escher, Bannikuppe S. Vishwanath, Felix J. Frey, K V Meyer |
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| Rok vydání: | 1995 |
| Předmět: |
medicine.medical_specialty
DNA Complementary Kidney Transfection Binding Competitive Cell Line chemistry.chemical_compound Endocrinology Mineralocorticoid receptor Furosemide In vivo Corticosterone Internal medicine medicine Animals Chemistry Hydroxysteroid Dehydrogenases In vitro Rats medicine.anatomical_structure Microsomes Liver Potassium Prednisone 11-beta-Hydroxysteroid Dehydrogenases Oxidation-Reduction Glucocorticoid medicine.drug |
| Zdroj: | Endocrinology. 136:1759-1765 |
| ISSN: | 1945-7170 0013-7227 |
| Popis: | 11 beta-hydroxysteroid dehydrogenase (11 beta-OHSD) protects the non-selective renal mineralocorticoid receptor from the endogeneous glucocorticoid cortisol. Thus, drugs inhibiting 11 beta-OHSD might enhance urinary loss of potassium. In an attempt to find drugs inhibiting 11 beta-OHSD, 23 commonly used agents known to interfere with the potassium metabolism have been screened for inhibitory effect on 11 beta-OHSD. Furosemide appeared as the only inhibitor. Its inhibition constant (Ki) was 19.5 microM when kidney and 21.3 microM when liver microsomes were used as a source of 11 beta-OHSD. The type of inhibition was competitive. For confirmation that furosemide specifically inhibits 11 beta-OHSD, the complementary DNA (cDNA) of 11 beta-OHSD was transfected into COS-1 cells devoid of spontaneous expression of 11 beta-OHSD. In these cells, oxidation of corticosterone (Ki = 17.4 microM) and reduction of dehydrocorticosterone (Ki = 12.5 microM) was inhibited by furosemide. To establish whether this inhibition also occurs in vivo, the 11 beta-hydroxysteroid prednisolone was administered with and without furosemide to rats. The concentration ratio of prednisolone to its 11-ketometabolite prednisone increased in kidney and liver tissue after furosemide administration, indicating inhibition of 11 beta-OHSD. These data suggest that furosemide modulates in vivo the access of 11 beta-OH glucocorticoids to their target organs. |
| Databáze: | OpenAIRE |
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