DIAZEPAM BINDING INHIBITOR PEPTIDE - CLONING AND GENE-EXPRESSION

Diazepam binding inhibitor (DBI) is a peptide, initially identified for its ability of displacing the binding of diazepam. The screening of lambda-gt 10 cDNA libraries from rat brain with a 47merdeoxyoligonucleotide probe, complementary to a small portion of DBI coding region, allowed the isolation of cDNA clones encoding the entire aminoacid sequence of DBI. This sequence, when compared to that of mouse, human and bovine, revealed that DBI is a well conserved peptide, suggesting a similar function in different species. In order to characterize the function of DBI, studies on the regulation of DBI gene expression were undertaken. The expression of DBI mRNA occurs unevenly in the brain, as well as in peripheral tissues. Moreover, the biosynthesis of DBI is up-regulated in the cerebellum and cerebral cortex of rats made tolerant to diazepam, suggesting that changes in the biosynthesis of DBI might be one of the mechanisms eliciting tolerance to benzodiazepine. In peripheral tissues, the expression of DBI mRNA changes during development. In liver, the content of DBI mRNA was found maximal at postnatal day 1. In contrast, in kidney and heart a linear increase in levels of DBI mRNA was observed from postnatal day 1 to the adult stage, where it reached its maximum level. The tissue specific regulation of DBI mRNA expression, both pharmacologically or developmentally, leads to the hypothesis that DBI might have different functions in different tissues. This would be in line with recent findings that DBI might be also involved in the regulation of an important step of cell metabolism.