Effect of antiglucocorticoids on dexamethasone-induced inhibition of uridine incorporation and cell lysis in isolated mouse thymocytes |
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| Authors: | D Duval S Durant F Homo-Delarche |
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| Institution: | 1. Department of Hematology, St. Jude Children''s Research Hospital, Memphis, TN;2. Department of Biomedicine and Prevention, PhD in Immunology, Molecular Medicine and Applied Biotechnology, University of Rome Tor Vergata, Rome, Italy;3. Departments of Pediatrics and Cancer Biology, Cleveland Clinic, Cleveland, OH;4. Division of Pediatric Hematology and Oncology, Department of Pediatrics and Adolescent Medicine, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany |
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| Abstract: | We have compared in isolated mouse thymocytes the action of progesterone, cortexolone, DXH (a 17-beta carboxamide derivative of dexamethasone) and RU 38486 (a new antiglucocorticoid molecule), on dexamethasone-induced inhibition of uridine incorporation and cell lysis, with the affinities of these drugs for glucocorticoid receptors. Our results show that progesterone, cortexolone and DXH which possess similar affinities for glucocorticoid receptors may exhibit variable, weak agonist and antagonist activities according to the parameter studied. RU 38486 was a potent competitor of dexamethasone and was able, when present in a 10-fold excess, to counteract almost completely the inhibitory action as well as the lytic action of 5 X 10(-8) M dexamethasone. This compound which exerts almost no agonist activity may therefore represent a useful tool to investigate the mode of action of antiglucocorticoids. |
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