The goal of this project is to understand aspects of the structure, function, and regulation of the genes encoding the mammalian counterparts to bombesin-like neuropeptides. Two mammalian bombesin-like peptides have been identified to date, gastrin-releasing peptide (MP and neuromedin B (NM-B). Both peptides are found in a subset of central and peripheral neurons, and share a structural motif at their carboxyl-terminal domains, which is necessary and sufficient for binding to high-affinity cell surface bombesin receptors. There are several subprojects being actively pursued: 1) CDNA and genomic clones for rat and human prepro-GRP and prepro-NMB genes have been isolated and characterized to identify potential regulatory motifs in the promoter regions. 2) in situ hybridization techniques are being utilized to determine the localization of GRP and NMB mRNA at the cellular level in brain; 3) Promoter-reporter gene constructs will be introduced into cultured cell hosts by transfection to map the elements in the promoter region of the human GRP gene responsible for the cell-type specific regulation.
