1. An unsaturated fatty acid, leukotriene C4 (LTC4), has a potent contractile effect on human airway smooth muscle, and has been implicated in the pathogenesis of human asthma. Using front-surface fluorometry with fura-PE3, the effect of LTC4 on the intracellular Ca2+ concentration ([Ca2+]i) and tension were investigated in porcine tracheal smooth muscle strips. 2. The application of LTC4 induced little or no contraction despite a small and transient increase in [Ca2+]i In the presence of LTC4, however, the contractions evoked by high K+ depolarization or a low concentration of carbachol (CCh) were markedly enhanced without inducing any changes in the [Ca2+]i levels, thus indicating that LTC4 increases the Ca2+ responsiveness of the contractile apparatus. This LTC4-induced increase in Ca2+ responsiveness could partly be reproduced in the permeabilized preparation of tracheal smooth muscle strips. 3. The LTC4-induced enhancement of contraction was accompanied by an increase in myosin light chain (MLC) phosphorylation and was blocked by a rho kinase inhibitor (Y-27632), but not by either a PKC inhibitor (calphostin C) or a tyrosine kinase inhibitor (genistein). 4. These results indicated that, in porcine tracheal smooth muscle, LTC4 enhances the contraction by increasing the Ca2+ responsiveness of the contractile apparatus in a MLC phosphorylation dependent manner, possibly through the activation of the rho-rho kinase pathway.
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