Adenosine stimulation of dna synthesis in human endothelial
cells.
Ethier, Michael F., and James G. Dobson.
Departments of Medicine and Physiology, University of
Massachusetts, Medical School, Worcester, Massachusetts 01655
APStracts 3:0510H, 1996.
Adenosine stimulation of DNA synthesis in human endothelial cells was
investigated by measuring [3H]thymidine incorporation in cultures
derived from human umbilical veins. After an 18 hr exposure to
adenosine in serum-free medium endothelial cell [3H]thymidine
incorporation was increased by 30%-64%. Adenosine-induced DNA
synthesis was not mimicked by adenosine receptor agonists and was not
inhibited by adenosine receptor antagonists. Adenosine-induced DNA
synthesis was inhibited 81% by 100 [mu]M 5'-(N,N-dimethyl) amiloride,
an inhibitor of Na+/H+ exchange, and was totally inhibited by 10
[mu]M 2',4'-dibromoacetophenone, an inhibitor of phospholipase A2
(PLA2). Adenosine increased cAMP levels in endothelial cells but
adenosine-induced DNA synthesis was not inhibited by the protein
kinase A (PKA) inhibitor Rp-cAMPs. Both ATP and the phorbol ester PMA
increased DNA synthesis in human endothelial cells. Stimulation by
ATP was inhibited by the P2 receptor antagonist suramin and PMA
stimulation was inhibited by the protein kinase C (PKC) inhibitor H7.
Neither suramin nor H7 inhibited adenosine-stimulated DNA synthesis.
The results suggest that Na+/H+ exchange and PLA2 are involved in
adenosine-induced DNA synthesis in cultures of human endothelial
cells independent of adenosine receptor, PKA or PKC activation.
Received 15 April 1996; accepted in final form 1 October 1996.
APS Manuscript Number H335-6.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 31 December 1996