Purification of a novel DBI processing product, DBI39-75, and characterization of its binding site in rat brain

This report describes the purification and characterization from rat brain of DBI39-75, a novel, biologically active processing product of diazepam binding inhibitor (DBI). We have shown that DBI39-75 in nM concentrations stimulates pregnenolone synthesis in mitochondria of rat brain. Using cross-linking of 125I-DBI39-75 in steroidogenically active concentrations we have demonstrated for the first time that the DBI fragment has a specific high affinity binding site in rat brain. Displacement of [3H]PK 11195 and [3H]Ro5-4864 by DBI39-75 indicates more complex interaction than the competitive inhibition. Collectively, the data suggest that the function of DBI39-75 is mediated through a mitochondrial receptor complex which includes binding sites for PK 11195 and Ro5-4864.