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Low Concentrations of Ouabain Activate Vascular Smooth Muscle Cell Proliferation
Author(s) -
ALLEN JULIUS C.,
ABRAMOWITZ JOEL,
KOKSOY ASLIHAN
Publication year - 2003
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/j.1749-6632.2003.tb07235.x
Subject(s) - ouabain , intracellular , microbiology and biotechnology , chemistry , vascular smooth muscle , transactivation , ion pump , caveolae , diaphragm pump , biophysics , gene isoform , signal transduction , sodium , biochemistry , biology , endocrinology , ion , smooth muscle , gene expression , materials science , organic chemistry , micropump , gene , nanotechnology
A bstract : In vascular smooth muscle cells the sodium pump complex can act as an intracellular signal transducing complex activated by low ouabain concentrations, which inhibit sufficient pumps to activate a transduction cascade via transactivation of EGFR, but insufficient pumps to alter intracellular ions. Higher concentrations interfere with proliferation. This biphasic ouabain response occurs in human, canine, and rat VSMC at concentrations that reflect the differing ouabain affinities of the α1 isoforms of the three species. This supports the proposal that this effect occurs via ouabain binding to the α1 subunit of the Na pump. These data suggest a new transducing function of ouabain‐Na pump interaction, distinct from the cellular ionic effects resulting from pump inhibition. This transducing function occurs at ouabain concentrations that do not perturb cytoplasmic ion content and requires specific localization of pumps to caveolae.