Methylprednisolone inhibits uptake of Ca2+ and Na+ ions into concanavalin A-stimulated thymocytes.
The glucocorticoid drug methylprednisolone inhibits respiration in concanavalin A-stimulated rat thymocytes at concentrations that are relevant to its acute clinical efficacy against autoimmune diseases and spinal cord injury. Methylprednisolone affects several processes, including ion cycling, substrate oxidation reactions and RNA/DNA synthesis. The inhibition of respiration used to drive ATP-consuming cycles of Ca2+ and Na+ ions across the plasma membrane has been proposed to be either primary or secondary to restriction of cellular ATP supply. By comparing the effects of methylprednisolone with those of myxothiazol, an inhibitor of the mitochondrial electron transport chain, we show that the effects of methylprednisolone on Ca2+ and Na+ cycling are primary. We propose that methylprednisolone acts by affecting membrane properties to inhibit Ca2+ and Na+ uptake across the plasma membrane and to increase H+ uptake across the mitochondrial membrane, and that other effects are secondary.
Buttgereit
F
F
Medizinische Klinik und Poliklinik III, Humboldt-Universität (Charité), Berlin, Federal Republic of Germany.
Krauss
S
S
Brand
M D
MD
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000037:antagonists & inhibitors* / Q000378:metabolism; D002478:Cells, Cultured; D003208:Concanavalin A / Q000494:pharmacology*; D003470:Culture Media / Q000494:pharmacology; D005260:Female; D008213:Lymphocyte Activation / Q000187:drug effects*; D008775:Methylprednisolone / Q000494:pharmacology*; D010101:Oxygen Consumption / Q000187:drug effects; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012964:Sodium / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism*
D003470:Culture Media; D011500:Protein Synthesis Inhibitors; D003208:Concanavalin A; D000255:Adenosine Triphosphate; D012964:Sodium; D002118:Calcium; D008775:Methylprednisolone