Nitric oxide increases protein tyrosine phosphatase activity in
aortic smooth muscle cells relationship to no-induced
antimitogenesis.
Dhaunsi, Gursev S., Carolyn Matthews, Kuljeet Kaur, and Aviv Hassid.
Department of Physiology and Biophysics, University of Tennessee,
894 Union Avenue, Memphis, TN 38163-0001
APStracts 3:0452H, 1996.
We investigated the mechanisms of NO-induced antimitogenesis in
primary aortic smooth muscle cells from newborn rats. SNAP, a NO
-releasing agent, decreased basal and growth factor-stimulated DNA
synthesis with a threshold effectiveness of 0.3 to 3 M. A second NO
-releasing agent, SIN-1, a hydrolysis resistant cyclic nucleotide, 8
-bromo-cGMP, and atrial natriuretic peptides elicited a similar
effect, whereas 8-bromo-cAMP was ineffective, supporting the view
that NO and cGMP, but not cAMP, mediated at least some of SNAPs
antimitogenic effect. SNAP and 8-bromo-cGMP decreased the levels of
phosphotyrosine, especially in proteins of 70 to 85 kDa and 215 kDa
molecular mass. SNAP decreased protein phosphotyrosine levels with a
threshold effectiveness similar to that of its antimitogenic effect.
Moreover, SNAP increased PTPase activity in cell homogenates,
indicating that phosphotyrosine dephosphorylation was likely to be
the result of increased PTPase activity. Peroxovanadate, a selective
PTPase inhibitor, blocked the antimitogenic effect of 8-bromo-cGMP,
suggesting that loss of protein phosphotyrosine and antimitogenesis
were causally linked. These findings describe a potential mechanism
for NO-induced antimitogenesis in aortic smooth muscle cells in
primary culture.
Received 9 July 1996; accepted in final form 11 September 1996.
APS Manuscript Number H605-6.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 5 November 1996