Figure 10.

Clinical effectiveness of Combination of β₂-adrenoceptor agonists and muscarinic receptor antagonists is in the treatment for COPD via Ca²⁺ signaling (Ca²⁺ dynamics and Ca²⁺ sensitization). Since addition of β₂-adrenoceptor agonists to muscarinic receptor antagonists markedly enhance an inhibition of airway smooth muscle contraction, combination of these two agents are useful to suppression of excessive stimulation to muscarinic receptors induced by acetylcholine production in the airways, which is an fundamental characteristic for COPD. This phenomenon is due to cross talk between these two receptors via K_Ca channel-induced Ca²⁺ dynamics and PKC-induced Ca²⁺ sensitization in airway smooth muscle. Therefore, this combination therapy leads to reducing symptoms such as dyspnea on exertion and frequency of exacerbations, and to improving health status and lung function in patients with COPD.