The long term goal of this proposal is to elucidate the mechanism of action of bombesin-like peptides (BLP) within the lungs by focusing on the characterization of novel BLP binding proteins isolated from lung. A growing body of evidence suggests that the BLP growth factor system plays an important role in lung development, response to injury, and carcinogenesis. As a major product of the pulmonary neuroendocrine cell, BLP are mitogenic for bronchial epithelial cells and fibroblasts. They appear to be involved in both lung growth and maturation. BLP have been implicated to play a role in the pathogenesis of selected lung diseases including: bronchopulmonary dysplasia, plexogenic pulmonary arteriopathy, eosinophilic granuloma, and small cell lung cancer. Recently BLP receptors have been cloned and appear to belong to a family of related receptors of the G protein-coupled receptor superfamily. However, these receptors have not been detected at the mRNA level in northern blots of lung. My preliminary studies provide strong evidence for the existence of previously undescribed BLP binding proteins in the lung. We hypothesize that BLP effects within the lungs are modulated by these BLP binding proteins, and that further characterization of the structure, expression, and function of these BLP binding proteins may elucidate the role of BLP in lung development and disease. We propose to examine the role of BLP in the lung by molecular cloning of these novel BLP binding proteins (Specific Aim 1), determining cell and tissue specific expression (Specific Aim 2), and defining the function of these novel BLP binding proteins (Specific Aim 3). These studies may be of therapeutic importance by suggesting new approaches to either augmenting lung development or interfering with the aberrant growth which occurs in fibrotic diseases and cancer.
