Arachidonic acid stimulates protein tyrosine phosphorylation in
vascular cells.
Buckley, Barbara J., and A. Richard Whorton.
Departments of Medicine and Pharmacology, Duke University Medical
Center, Durham, NC 27710
APStracts 2:0224C, 1995.
Arachidonic acid and its metabolites are important cellular mediators.
In this study, we report a novel role for arachidonic acid in
vascular cell signalling. We tested the effects of exogenous
arachidonic acid on protein tyrosine phosphorylation in cultured
vascular endothelial and smooth muscle cells. Arachidonic acid
stimulated the phosphorylation of tyrosine-containing proteins of
approximately 58, 93 and 120 kDa in the three cell types studied.
This response was dose-dependent with a maximum effect observed with
40 NM arachidonic acid. Phosphorylation was rapid and transient,
reaching a peak 0.5 min following the addition of arachidonic acid
and returning to baseline by 8 min. A common set of protein
substrates was phosphorylated in smooth muscle cells treated with the
Ca2+-mobilizing agonist endothelin, concommitant with an increase in
endogenous unesterified arachidonic acid. In order to determine
whether the protein tyrosine phosphorylation was due to arachidonic
acid or to a metabolite, we used inhibitors of cyclooxygenase,
lipoxygenase and epoxygenase pathways. Ibuprofen,
nordihydroguaiaretic acid, eicosatriynoic acid and eicosatetraynoic
acid and 8-methoxypsoralen failed to inhibit the arachidonic acid
-mediated response. We also found increased protein tyrosine
phosphorylation following treatment with oleic, linolenic and
[delta]-linoleic acid. These results suggest a mechanism of protein
tyrosine phosphorylation that is directly stimulated by unmetabolized
unsaturated fatty acids.
Received 6 March 1995; accepted in final form 26 May 1995.
APS Manuscript Number C122-5.
Article publication pending Am. J. Physiol. (Cell Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 8 June 1995.