INHIBITION OF DEXAMETHASONE BINDING TO HUMAN GLUCOCORTICOID RECEPTOR BY NEW-WORLD PRIMATE CELL-EXTRACTS

To determine if New World primates express an inhibitor that influence s glucocorticoid receptor (GR) binding characteristics, we examined [H -3]dexamethasone binding in cytosol prepared from B95-8 lymphoid cells , derived from the cotton top tamarin (Saguinus oedipus), in combinati on with cytosol prepared from human or rat tissues. B95-8 cytosol inhi bited specific binding of [H-3]dexamethasone (P < 0.01) when mixed wit h cytosol prepared from either a human lymphoid cell line (HL) or rat thymus. The inhibitory activity was heat labile and trypsin sensitive. Peak inhibitory activity was found in the 150-200 kd fractions after Sephacryl G-200 ultrafiltration. Scatchard analysis of [H-3]dexamethas one binding using mixed cytosol showed a diminished GR apparent bindin g affinity when compared to HL cytosol. Kinetic studies using mixed cy tosol indicated that B95-8 cytosol did not affect the apparent dissoci ation rate of [H-3]dexamethasone. These data demonstrate that B95-8 ce lls contain a competitive inhibitor that prevents binding of dexametha sone to its cognate receptor.