Alteration of structural order of human erythrocyte ghost membrane by glucocorticoids and the influence of the glucocorticoid receptor antagonist RU 486
Moldenhauer, I.; Lasch, J.; Hirschelmann, R.
International Journal of Tissue Reactions 16(3): 113-119
1994
ISSN/ISBN: 0250-0868 PMID: 7852032 Document Number: 289824
High-dose pulse glucocorticoid therapy has been used successfully in the clinic in severe pathological conditions for about 20 years. The mode of glucocorticoid action after administration of such megadoses is inexplicable up to now. It is supposed that some effects may be due to membrane alterations. In the present in-vitro experiments the effect of dexamethasone, of further glucocorticoids, and of the glucocorticoid receptor antagonist RU 486, on structural order of human erythrocyte ghost membranes was investigated by determining the steady-state fluorescence anisotropy of diphenylhexatriene (DPH). Dexamethasone was found to induce a significant decrease in membrane structural order at concentrations of about 10(-6) M in a concentration-dependent manner. We found a correlation between the uptake of dexamethasone by the ghost membranes and the decrease in the structural order. The other glucocorticoids tested, methylprednisolone and corticosterone, were also effective at concentrations of 10(-5) M or greater. We observed no change in membrane structural order with RU 486 up to a concentration of 10(-4) M. However, simultaneous incubation of RU 486 with dexamethasone caused a distinct interference of RU 486 with dexamethasone. Thus, the glucocorticoid-induced membrane perturbation, the possibility to inhibit it by RU 486, and the inactivity of the structurally related progesterone, refer to relatively specific binding sites for the glucocorticoids in the membrane of erythrocyte ghosts.