Rifampicin Is Not an Activator of Glucocorticoid Receptor
| Autor: | G. M. Wochnik, Marcus C. Rosenhagen, Alexandra S. Herr, Florian Holsboer, Theo Rein |
|---|---|
| Rok vydání: | 2000 |
| Předmět: |
medicine.medical_specialty
ATP Binding Cassette Transporter Subfamily B Hydrocortisone Transcription Genetic Cell Pharmacology Biology Ligands Hippocampus Dexamethasone Mice Transactivation Receptors Glucocorticoid Glucocorticoid receptor Internal medicine Cyclosporin a polycyclic compounds medicine Animals Humans Drug Interactions Promoter Regions Genetic Antibiotics Antitubercular Cells Cultured Neurons Reporter gene Activator (genetics) bacterial infections and mycoses Endocrinology medicine.anatomical_structure Molecular Medicine Rifampin Rifampicin medicine.drug |
| Zdroj: | Europe PubMed Central |
| ISSN: | 1521-0111 0026-895X |
| DOI: | 10.1124/mol.57.4.732 |
| Popis: | Rifampicin, an antibiotic widely used in tuberculosis therapy, is known to exert psychotropic side effects in some patients. Recently, rifampicin has been reported to activate the glucocorticoid receptor (GR) in human hepatocytes. Because there is evidence that increased levels of glucocorticoids may induce cognitive impairment, sometimes culminating in depression, the side effects of rifampicin may result from GR activation in central nerve cells. Therefore, we used reporter gene assays to determine whether rifampicin displays glucocorticoid-like effects in human neuroblastoma SK-N-MC cells or mouse hippocampal HT22 cells. Rifampicin was unable to elicit any detectable transactivation of GR in both cell types, whereas cortisol or dexamethasone led to a potent transcriptional response. Rifampicin was also inactive in the same HepG2 cell line that was originally used to demonstrate the effect of rifampicin on GR. Moreover, rifampicin was unable to compete with dexamethasone for binding to GR. Finally, by blocking the multidrug resistance P-glycoprotein transporter (a xenobiotic extrusion pump) with verapamil or cyclosporin A, we excluded the possibility that the lack of effect by rifampicin was due to its export from the cell. Our results establish that rifampicin does not activate GR, and rule out the hypothesis that the psychotropic side effects of rifampicin treatment are a consequence of GR activation. |
| Databáze: | OpenAIRE |
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