Crosstalk between Gi and Gq/Gs pathways in airway smooth muscle regulates bronchial contractility and relaxation.

Receptor-mediated airway smooth muscle (ASM) contraction via G(alphaq), and relaxation via G(alphas), underlie the bronchospastic features of asthma and its treatment. Asthma models show increased ASM G(alphai) expression, considered the basis for the proasthmatic phenotypes of enhanced bronchial hyperreactivity to contraction mediated by M(3)-muscarinic receptors and diminished relaxation mediated by beta(2)-adrenergic receptors (beta(2)ARs). A causal effect between G(i) expression and phenotype has not been established, nor have mechanisms whereby G(i) modulates G(q)/G(s) signaling.

Transcriptional response to persistent beta2-adrenergic receptor signaling reveals regulation of phospholamban, which alters airway contractility.

Beta(2)-Adrenergic receptors (beta(2)AR) are expressed on airway smooth muscle cells and act to relax the airway on activation by beta-agonists. These agents are utilized for treating asthma but are associated with adverse outcomes. To ascertain the effects of persistent beta(2)AR activation on gene expression, cultured airway smooth muscle cells derived from wild-type (WT) and transgenic mice overexpressing beta(2)AR were subjected to DNA microarray analysis; 319 genes were increased and 164 were decreased.