Leukotriene C-4 enhances the contraction of porcine tracheal smooth musclethrough the activation of Y-27632, a rho kinase inhibitor, sensitive pathway

1 An unsaturated fatty acid, leukotriene C-4 (LTC4), has a potent contracti le effect on human airway smooth muscle, and has been implicated in the pat hogenesis of human asthma. Using front-surface fluorometry with fura-PE3, t he effect of LTC4 on the intracellular Ca2+ concentration ([Ca2+](i)) and t ension 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 KC depolarization or a low concentration of car bachol (CCh) were markedly enhanced without inducing any changes in the [Ca 2+](i) levels, thus indicating that LTC4 increases the Ca2+ responsiveness of the contractile apparatus. This LTC4-induced increase in Ca2+ responsive ness could partly be reproduced in the permeabilized preparation of trachea l smooth muscle strips. 3 The LTC4-induced enhancement of contraction was accompanied by an increas e in myosin light chain (MLC) phosphorylation and was blocked by a rho kina se 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 enh ances the contraction by increasing the Ca2+ responsiveness of the contract ile apparatus in a MLC phosphorylation dependent manner, possibly through t he activation of the rho-rho kinase pathway.