Actin reorganization in airway smooth muscle cells involves Gq and Gi-2 activation of Rho

Am J Physiol. 1999 Sep;277(3):L653-61. doi: 10.1152/ajplung.1999.277.3.L653.

Abstract

Extracellular stimuli induce cytoskeleton reorganization (stress-fiber formation) in cells and Ca2+ sensitization in intact smooth muscle preparations by activating signaling pathways that involve Rho proteins, a subfamily of the Ras superfamily of monomeric G proteins. In airway smooth muscle, the agonists responsible for cytoskeletal reorganization via actin polymerization are poorly understood. Carbachol-, lysophosphatidic acid (LPA)-, and endothelin-1-induced increases in filamentous actin staining are indicative of actin reorganization (filamentous-to-globular actin ratios of 2.4 +/- 0.3 in control cells, 6.7 +/- 0.8 with carbachol, 7.2 +/- 0.8 with LPA, and 7.4 +/- 0.9 with endothelin-1; P < 0.001; n = 14 experiments). Although the effect of all agonists was blocked by C3 exoenzyme (inactivator of Rho), only carbachol was blocked by pertussis toxin. Although carbachol-induced actin reorganization was blocked in cells pretreated with antisense oligonucleotides directed against Galphai-2 alone, LPA- and endothelin-1-induced actin reorganization were only blocked when both Galphai-2 and G(q)alpha were depleted. These data indicate that in human airway smooth muscle cells, carbachol induces actin reorganization via a Galphai-2 pathway, whereas LPA or endothelin-1 induce actin reorganization via either a Galphai-2 or a Gqalpha pathway.

MeSH terms

  • ADP Ribose Transferases / pharmacology
  • Actins / drug effects
  • Actins / metabolism
  • Actins / physiology*
  • Botulinum Toxins*
  • Carbachol / antagonists & inhibitors
  • Carbachol / pharmacology
  • Endothelin-1 / antagonists & inhibitors
  • Endothelin-1 / pharmacology
  • GTP-Binding Proteins / genetics
  • GTP-Binding Proteins / physiology*
  • Humans
  • Lysophospholipids / antagonists & inhibitors
  • Lysophospholipids / pharmacology
  • Muscle, Smooth / cytology
  • Muscle, Smooth / metabolism*
  • Oligonucleotides, Antisense / pharmacology
  • Pertussis Toxin
  • Trachea / cytology
  • Trachea / metabolism*
  • Virulence Factors, Bordetella / pharmacology
  • ras Proteins / physiology*

Substances

  • Actins
  • Endothelin-1
  • Lysophospholipids
  • Oligonucleotides, Antisense
  • Virulence Factors, Bordetella
  • Carbachol
  • ADP Ribose Transferases
  • exoenzyme C3, Clostridium botulinum
  • Pertussis Toxin
  • Botulinum Toxins
  • GTP-Binding Proteins
  • ras Proteins