INCREASED CA2+ AND MYOSIN PHOSPHORYLATION, BUT NOT CALMODULIN ACTIVITY IN SENSITIZED AIRWAY SMOOTH MUSCLES

The increased shortening velocity and capacity of airway smooth muscle (ASM) from ragweed pollen-sensitized dogs, which may be responsible f or its in vivo airway hyperresponsiveness, have been shown to be assoc iated with higher actomyosin adenosinetriphosphatase activity and grea ter level of phosphorylation of the 20-kDa myosin light-chain (MLC(20) ) at rest and during contraction. Current studies show that the elevat ed level of phosphorylation may be the result of an increased myosin l ight-chain kinase (MLCK) activity due to excessive quantity of MLCK. T here were no significant changes in total activity of calmodulin, a pr otein that binds and activates MLCK, in sensitized dog ASM (SASM) comp ared with control ASM (CASM). When normalized to the relative calmodul in content in the tissues, the specific calmodulin activities (means /- SE) in sensitized tracheal smooth muscle (STSM) and sensitized bron chial smooth muscle (SBSM) and in their controls were not different (S TSM 0.359 +/- 0.117, CTSM 0.339 +/- 0.136, SBSM 0.201 +/- 0.098, and c ontrol bronchial smooth muscle 0.213 +/- 0.056 nmol P-i . calmodulin c ontent(-1). min(-1), respectively). Intracellular Ca2+ levels indicate d by fura 2 fluorescent dye remained unaltered in SASM. We conclude th at airway hyperresponsiveness may result from higher MLCK content in S ASM rather than from changes in Ca2+-calmodulin activities, which is a n example of alteration in Ca2+ sensitivity of ASM.