Adenosine stimulation of DNA synthesis in human endothelial cells.
We investigated adenosine stimulation of DNA synthesis in human endothelial cells by measuring [3H]thymidine incorporation in cultures derived from human umbilical veins. After 18 h of 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 microM 5'-(N,N-dimethyl)amiloride, an inhibitor of Na+/H+ exchange, and was totally inhibited by 10 microM 2',4'-dibromoacetophenone, an inhibitor of phospholipase A2 (PLA2). Adenosine increased adenosine 3',5'-cyclic monophosphate 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 4beta-phorbol 12-myristate 13-acetate (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 H-7. Neither suramin nor H-7 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 independently of adenosine receptor, PKA, or PKC activation.
Ethier
M F
MF
Department of Medicine, University of Massachusetts Medical School, Worcester 01655, USA.
Dobson
J G
JG
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000494:pharmacology; D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000241:Adenosine / Q000494:pharmacology*; D000255:Adenosine Triphosphate / Q000494:pharmacology; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D004247:DNA / Q000096:biosynthesis*; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D011061:Poly A / Q000494:pharmacology; D058915:Purinergic P1 Receptor Antagonists; D011799:Quinazolines / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013868:Thioinosine / Q000031:analogs & derivatives / Q000494:pharmacology; D013873:Thionucleotides / Q000494:pharmacology; D013936:Thymidine / Q000378:metabolism; D014230:Triazoles / Q000494:pharmacology; D014471:Umbilical Veins
D058915:Purinergic P1 Receptor Antagonists; D011799:Quinazolines; D013873:Thionucleotides; D014230:Triazoles; D005576:Colforsin; C016957:adenosine-3',5'-cyclic phosphorothioate; D011061:Poly A; D013868:Thioinosine; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000255:Adenosine Triphosphate; D004247:DNA; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; C001789:4-nitrobenzylthioinosine; D000241:Adenosine; D013755:Tetradecanoylphorbol Acetate; D015056:1-Methyl-3-isobutylxanthine; D013936:Thymidine; C052410:9-chloro-2-(2-furyl)-(1,2,4)triazolo(1,5-c)quinazolin-5-imine