Leukotriene D(4)-induced Rho-mediated actin reorganization in human bronchial smooth muscle cells.
We investigated the role of cysteinyl leukotriene (CysLT) receptors on leukotriene D(4)-induced actin reorganization and the signaling pathways of the response in human bronchial smooth muscle cells. The effects of leukotriene D(4) on actin reorganization in human bronchial smooth muscle cells were evaluated by dual-fluorescence labeling of filamentous (F) and monomeric (G) actin with fluorescein isothiocyanate (FITC)-labeled phalloidin and Texas Red-labeled DNase I, respectively. Leukotriene D(4) (100 nM) induced actin reorganization in the presence and absence of extracellular Ca(2+). The CysLT type 1 (CysLT(1)) receptor antagonist ONO 1078 (4-oxo-8(-)[p-(4-phenylbutyloxy) benzoylamino]-2-(tetrazol-5-yl)-4H-1-benzopyran hemihydrate) inhibited leukotriene D(4)-induced actin reorganization. Pretreatment with pertussis toxin, C3 exoenzyme, or tyrosine kinase inhibitors significantly reduced leukotriene D(4)-induced actin reorganization. However, phosphatidylinositol-3-kinase and protein kinase C inhibitors had little effect on these responses. These results suggest that leukotriene D(4)-induced actin reorganization in human bronchial smooth muscle cells is extremely dependent on the CysLT(1) receptor coupled with pertussis toxin-sensitive G protein, Rho GTPases and tyrosine phosphorylation pathways.
Saegusa
S
S
Department of Comparative Pathophysiology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo, Tokyo 113-8657, Japan.
Tsubone
H
H
Kuwahara
M
M
D036002:ADP Ribose Transferases / Q000494:pharmacology; D000199:Actins / Q000187:drug effects* / Q000378:metabolism; D001905:Botulinum Toxins; D001980:Bronchi / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D002867:Chromones / Q000494:pharmacology; D016650:Fluorescein-5-isothiocyanate; D005456:Fluorescent Dyes; D019204:GTP-Binding Proteins / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D020024:Leukotriene Antagonists / Q000494:pharmacology; D017998:Leukotriene D4 / Q000494:pharmacology*; D008565:Membrane Proteins; D009130:Muscle, Smooth / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D037342:Pertussis Toxin; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D018077:Receptors, Leukotriene / Q000187:drug effects* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D014443:Tyrosine / Q000378:metabolism; D010566:Virulence Factors, Bordetella / Q000494:pharmacology; D014966:Xanthenes; D020741:rho GTP-Binding Proteins / Q000187:drug effects* / Q000378:metabolism
D000199:Actins; D002867:Chromones; D005456:Fluorescent Dyes; D020024:Leukotriene Antagonists; D008565:Membrane Proteins; D018077:Receptors, Leukotriene; D010566:Virulence Factors, Bordetella; D014966:Xanthenes; D014443:Tyrosine; D017998:Leukotriene D4; C034657:Texas red; C412375:cysteinyl leukotriene receptor 2; D036002:ADP Ribose Transferases; C063007:exoenzyme C3, Clostridium botulinum; D037342:Pertussis Toxin; D011505:Protein-Tyrosine Kinases; D001905:Botulinum Toxins; D019204:GTP-Binding Proteins; D020741:rho GTP-Binding Proteins; D016650:Fluorescein-5-isothiocyanate; C083169:leukotriene D4 receptor; C047681:pranlukast