Transgenic techniques to delineate cell-specific effects of beta2-adrenergic receptors in the lung.

Abstract

Many, if not most, of the different cell types within the lung have been shown to express beta(2)-adrenergic receptors (beta(2)ARs) on the cell surface. beta(2)ARs have thus been implicated in the regulation of many aspects of lung function. However, the physiologic and therapeutic relevance for many of these cell-specific responses has been difficult to establish because of confounding effects that result from the simultaneous activation of receptors on multiple cell types in an in vivo environment. It has been recognized in in vitro models that overexpression of G-protein-coupled receptors such as the beta(2)ARs can increase the number of spontaneously active receptors (R*) and thereby promote autonomous signal transduction or enhanced agonist sensitivity. With transgenic techniques, high levels of receptor expression and activation can also be attained in vivo. By further using cell-specific promoters to direct expression, it is possible to express beta(2)ARs in select cell types of a heterogeneous organ such as the lung. In this manner, activation of receptor signaling is limited to the targeted cell. Promoter-directed transgenesis can therefore be a useful tool to delineate cell-specific beta(2)AR-mediated effects in the lung.