Modulation of Nb2 cell mitogenesis by peripheral benzodiazepine ligands

Abstract

In this study, we investigated the effects of the peripheral benzodiazepine ligands, Ro5-4864 (putative antagonist) and PK 11195 (putative antagonist) on prolactin stimulated mitogenesis in Nb2 cells. Ro5-4864 and PK 11195 at 10⁻⁹ M maximally enhanced prolactin stimulated mitogenesis. At 10⁻⁶ M Ro5-4864 inhibited prolactin stimulated mitogenesis. Clonazepam, a ligand for the central benzodiazepine receptor had no effect on mitogenesis. Interaction studies were undertaken to determine if Ro5-4864 and PK 11195 act on the same site. The ability of each ligand to enhance the mitogenic action of prolactin was blocked by a 10⁻⁶ M concentration of the other ligand. Finally, simultaneous addition of 10⁻⁹ M of the ligands resulted in no additive effect over each ligand alone. These data show that peripheral benzodiazepine ligands modulate prolactin-stimulated mitogenesis and suggests they interact at the same binding site.