BOMBESIN LIKE PEPTIDES IN LUNG DEVELOPMENT

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Immature lung development continues to be a major cause of morbidity and mortality in premature infants. The purpose of this project is to characterize the role of bombesin-like peptides in lung development. The bombesin-like peptides are a large family of peptides originally characterized in frog skin, but later found to have wide distribution and potent physiologic effects in mammals. One mammalian homolog of bombesin is gastrin-releasing peptide (GRP). The well documented expression of GRP in developing human lung and the ability of GRP to stimulate cellular growth has led to the hypothesis that GRP plays a critical role in lung development. Because of the lack of good animal models, it has not previously been possible to accurately determine the role of GRP in lung development. The recent demonstration in our laboratory that GRP expression in fetal monkey lung is strikingly similar to that of humans now provides an excellent animal model to characterize the role of GRP in human lung development. Complicating the effects of bombesin-like peptides on lung development is evidence suggesting that in utero exposure to nicotine stimulates fetal GRP expression. We have now developed methods to administer GRP in utero to fetal monkeys, methods to administer nicotine to the mothers to simulate maternal smoking, and suitable morhometric, histologic and molecular techniques to determine the effects of these treatments on lung development. Results from these studies could have important implications for the use of bombesin-like peptides to stimulate lung development.