Fig. 1. Signal transduction and intracellular concentration of free Ca2+([Ca2+]i) regulation in an airway smooth muscle cell. When the muscarinic receptor (M3) is stimulated, voltage-dependent Ca2+channels (VDCCs) are activated, and Ca2+enters the cytosol through the channels. Similarly, a G protein (Gq) is activated by the muscarinic receptor and in turn activates phospholipase C (PLC), resulting in the rapid breakdown of phosphatidylinositol 4,5-bisphosphate (PIP2) to inositol 1,4,5-triphosphate (IP3) and diacylglycerol (DAG). While DAG activates protein kinase C (PKC), IP3mobilizes Ca2+from the sarcoplasmic reticulum (SR). On the other hand, adenylate cyclase (AC) is activated by the β2-adrenergic receptor via a G protein (Gs), resulting in the breakdown of adenosine triphosphate (ATP) to cyclic adenosine monophosphate (AMP). Cyclic AMP activates protein kinase A (PKA), resulting in a decrease in [Ca2+]iby stimulation of Ca2+efflux and stimulation of Ca2+uptake into the SR. Although stimulation of the M2receptor is known to inhibit AC via an inhibitory G protein (Gi), resulting in the reduction of cyclic AMP levels, the effect of PKC activation on Ca2+sensitivity or contractile elements is controversial .3,6