Mechanism of nicotine action in developing lung

This project will explore the mechanism underlying the developmental effects of nicotine in the lung by comparing four strains of mice that differ in nicotine response or in the presence or absence of a functional a7 nicotine receptor. We will examine the hypothesis that nicotine acts through a7 receptors located on the cells that line the developing airways causing these cells to make more GRP. The increased GRP would then cause the effects associated with nicotine exposure. Locations and levels of a7 receptors and GRP in developing lungs will be compared in the four mouse strains. Isolated embryonic mouse lungs grown in culture will be used to test whether blocking the action of GRP will also block the effect of nicotine. Elements of our proposed mechanism will also be examined in embryonic and fetal mouse lungs exposed to nicotine via the maternal drinking water.

Insights gained from this study will contribute to our understanding of how nicotine exerts its adverse effects on fetal lung development. Since we know that nicotine receptors and GRP are also present in adult lungs, the information gained about mechanisms of nicotine action in developing lung may also contribute to our understanding of tobacco-related lung diseases in adult smokers. It is hoped that increased understanding of underlying disease mechanisms may help identify new treatments and new methods of prevention.