Purification of a novel DBI processing product, DBI 39–75, and characterization of its binding site in rat brain

Abstract

This report describes the purification and characterization from rat brain of DBI 39–75, a novel, biologically active processing product of diazepam binding inhibitor (DBI). We have shown that DBI 39–75 in nM concentrations stimulates pregnenolone synthesis in mitochondria of rat brain. Using cross-linking of 125I-DBI 39–75 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 DBI 39–75 indicates more complex interaction than the competitive inhibition. Collectively, the data suggest that the function of DBI 39–75 is mediated through a mitochondrial receptor complex which includes binding sites for PK 11195 and Ro5-4864.