These results revealed an unanticipated beneficial therapeutic effect of beta-agonists, PLN downregulation, which acts to diminish airway hyperreactivity. Agents that inhibit PLN, and thus decrease constrictive responses, may act synergistically with the bronchodilating action of beta-agonists. A number of other genes related to [Ca2+]I are also differentially regulated by beta2AR activity some of which may act to oppose, or augment, the therapeutic efficacy of chronic beta-agonists. These genes or pathways may also represent additional targets in the treatment of asthma and related obstructive lung diseases. Keywords: genetic modification Overall design: To ascertain the effects of persistent beta2AR activation on gene expression, cultured airway smooth muscle cells derived from wild-type and transgenic mice overexpressing beta2AR were subjected to DNA microarray analysis