METHYLPREDNISOLONE INHIBITS UPTAKE OF CA2-STIMULATED THYMOCYTES( AND NA+ IONS INTO CONCANAVALIN A)

The glucocorticoid drug methylprednisolone inhibits respiration in con canavalin A-stimulated rat thymocytes at concentrations that are relev ant to its acute clinical efficacy against autoimmune diseases and spi nal cord injury. Methylprednisolone affects several processes, includi ng ion cycling, substrate oxidation reactions and RNA/DNA synthesis. T he inhibition of respiration used to drive ATP-consuming cycles of Ca2 + and Na+ ions across the plasma membrane has been proposed to be eith er primary or secondary to restriction of cellular ATP supply. By comp aring 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 propert ies to inhibit Ca2+ and Na+ uptake across the plasma membrane and to i ncrease H+ uptake across the mitochondrial membrane, and that other ef fects are secondary.