Down-regulation of G-protein-mediated Ca2+ sensitization in smooth muscle

Mol Biol Cell. 1997 Feb;8(2):279-86. doi: 10.1091/mbc.8.2.279.


Prolonged treatment with guanosine 5'-[gamma-thio]triphosphate (GTP gamma S; 5-16 h, 50 microM) of smooth muscle permeabilized with Staphylococcus aureus alpha-toxin down-regulated (abolished) the acute Ca2+ sensitization of force by GTP gamma S, AIF-4, phenylephrine, and endothelin, but not the response to phorbol dibutyrate or a phosphatase inhibitor, tautomycin. Down-regulation also abolished the GTP gamma S-induced increase in myosin light chain phosphorylation at constant [Ca2+] and was associated with extensive translocation of p21rhoA to the particulate fraction, prevented its immunoprecipitation, and inhibited its ADP ribosylation without affecting the immunodetectable content of G-proteins (p21rhoA, p21ras, G alpha q/11, G alpha i3, and G beta) or protein kinase C (types alpha, beta 1, beta 2, delta, epsilon, eta, theta, and zeta). We conclude that the loss of GTP gamma S- and agonist-induced Ca2+ sensitization through prolonged treatment with GTP gamma S is not due to a decrease in the total content of either trimeric (G alpha q/11, G alpha i3, and G beta) or monomeric (p21rhoA and p21ras) G-protein or protein kinase C but may be related to a structural change of p21rhoA and/or to down-regulation of its (yet to be identified) effector.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Aluminum Compounds / pharmacology
  • Animals
  • Antifungal Agents / pharmacology
  • Bacterial Toxins / pharmacology
  • Calcium / metabolism*
  • Detergents
  • Down-Regulation*
  • Endothelins / pharmacology
  • Fluorides / pharmacology
  • GTP-Binding Proteins / metabolism*
  • Guanosine 5'-O-(3-Thiotriphosphate) / pharmacology*
  • Hemolysin Proteins / pharmacology
  • In Vitro Techniques
  • Male
  • Muscle, Smooth, Vascular / drug effects*
  • Muscle, Smooth, Vascular / metabolism
  • Myosin Light Chains / metabolism
  • Phenylephrine / pharmacology
  • Phorbol 12,13-Dibutyrate / pharmacology
  • Phosphoric Monoester Hydrolases / antagonists & inhibitors
  • Phosphorylation
  • Portal Vein / drug effects
  • Portal Vein / metabolism
  • Precipitin Tests
  • Protein Kinase C / metabolism
  • Proto-Oncogene Proteins p21(ras) / metabolism
  • Pyrans*
  • Rabbits
  • Solubility
  • Spiro Compounds*
  • Time Factors
  • rhoA GTP-Binding Protein


  • Aluminum Compounds
  • Antifungal Agents
  • Bacterial Toxins
  • Detergents
  • Endothelins
  • Hemolysin Proteins
  • Myosin Light Chains
  • Pyrans
  • Spiro Compounds
  • staphylococcal alpha-toxin
  • tautomycin
  • Phenylephrine
  • tetrafluoroaluminate
  • Phorbol 12,13-Dibutyrate
  • Guanosine 5'-O-(3-Thiotriphosphate)
  • Protein Kinase C
  • Phosphoric Monoester Hydrolases
  • GTP-Binding Proteins
  • Proto-Oncogene Proteins p21(ras)
  • rhoA GTP-Binding Protein
  • Fluorides
  • Calcium