1. The contractile activation properties of human isolated bronchial smooth muscle were investigated using chemically (beta-escin) skinned strips. 2. Concentration-dependent contractions were induced by free ion concentrations of Ca2+ (0.5-3 microM), Sr2+ (2-200 microM) and Ba2+ (50-1000 microM). The resulting -log[cation]-tension relationships were fitted by sigmoidal curves with EC50 values (cation concentration required to produce half-maximal tension) and co-operativity factors (Hill coefficient, nH) of, respectively, 0.25 microM and 3.4 for Ca2+, 12 microM and 2.64 for Sr2+ and 100 microM and 1.73 for Ba2+. Maximal responses to Sr2+ and Ba2+ were 125.5 +/- 15.4 and 96 +/- 8.1% (n = 5) respectively of the maximum tension induced by Ca2+. 3. Trifluoperazine (5-100 microM), cyclic AMP (50-300 microM) and cyclic GMP (50-100 microM) each antagonized Ca2+ in a concentration-dependent manner. On the other hand, okadaic acid (OA, 0.2-1 microM) potentiated Ca2+ and increased the maximum response to Ca2+ (+25 +/- 5.4%, n = 5, for 1 microM OA). 4. This study has demonstrated the high Ca2+ sensitivity of the activation mechanism of human isolated bronchial smooth muscle. It also suggests that control of the contractile machinery in the human bronchus involves processes of phosphorylation and dephosphorylation. The beta-escin-treated human bronchus may be a useful model for investigating the cellular basis of some pathophysiological processes such as bronchial hyper-responsiveness.
展开▼
