Enhanced Myosin Phosphatase and Ca2+-Uptake Mediate Adrenergic Relaxation of Airway Smooth Muscle

We examined the mechanisms underlying relaxations evoked by isoproterenol (Iso) in isolated porcine, bovine, or human tracheal and bronchial tissues (TSM and BSM, respectively). Iso had little effect against contractions evoked by high KCl, indicating that it does not directly suppress voltage-dependent Ca2+-influx nor directly inhibit myosin light chain kinase. Furthermore, Iso was equally potent against carbachol (CCh) contractions in the presence versus absence of nifedipine (10−6 M), establishing that the primary action of Iso is not through membrane hyperpolarization. However, Iso relaxations in porcine/bovine BSM were significantly suppressed by inhibitors of the internal Ca2+ pump (cyclopiazonic acid; 10−5 M) or of myosin light chain phosphatase (calyculin; 10−6 M). Myosin light chain phosphatase activity was assayed directly (using 32P-labeled myosin) and found to be enhanced in a time- and concentration-dependent fashion by Iso. Iso relaxations in human airway tissues, on the other hand, were not...