title: Effects of adenine nucleotides on the proliferation of aortic endothelial cells.
abstract: The effects of adenine nucleotides and adenosine on DNA synthesis and cell growth have been studied in bovine aortic endothelial cells (BAECs). ATP produced a small but significant (+44%) increase of the fraction of BAECs whose nuclei are labeled by [3H]thymidine. This mitogenic effect was mimicked by ADP, the phosphorothioate analogues ATP gamma S and ADP beta S, and the nonhydrolyzable analogue adenosine 5'-(beta, gamma-imido)triphosphate (APPNP), whereas adenosine 5'-(alpha, beta-methylene)triphosphate (APCPP), a selective agonist of P2x-purinoceptors, had no effect at 10 microM and a small one at 100 microM; this profile is consistent with the involvement of P2y-receptors. Adenosine induced a mitogenic response of a magnitude similar to that of ATP. This effect was not reproduced by R-phenylisopropyl adenosine, by 5'-N-ethylcarboxamide adenosine, or by 2',5'-dideoxyadenosine, selective ligands of the A1- and A2-receptors and the P site, respectively, nor was it inhibited by 8-phenyltheophylline, an antagonist of both A1- and A2-receptors. The mechanism of this adenosine action thus remains unclear. ATP and ATP gamma S did not enhance the proliferation of BAECs cultured in the presence of fetal calf serum concentrations ranging from 0.5% to 10%. They inhibited the growth-promoting effect of basic fibroblast growth factor; among the various nucleotides tested, APCPP was the least effective to reproduce the action of ATP, suggesting the possible involvement of P2y-receptors.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Institute of Interdisciplinary Research, School of Medicine, Free University of Brussels, Belgium.
authors.forename: P
authors.initials: P
authors.lastname: Van Daele
authors.forename: A
authors.initials: A
authors.lastname: Van Coevorden
authors.forename: P P
authors.initials: PP
authors.lastname: Roger
authors.forename: J M
authors.initials: JM
authors.lastname: Boeynaems
mesh_terms: D000227:Adenine Nucleotides / Q000494:pharmacology*; D000241:Adenosine / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D001011:Aorta; D002417:Cattle; D002455:Cell Division / Q000187:drug effects*; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis / Q000187:drug effects; D004730:Endothelium, Vascular / Q000166:cytology* / Q000187:drug effects; D005346:Fibroblast Growth Factors / Q000037:antagonists & inhibitors; D011983:Receptors, Purinergic / Q000502:physiology
chemical_list: D000227:Adenine Nucleotides; D011983:Receptors, Purinergic; D005346:Fibroblast Growth Factors; D000255:Adenosine Triphosphate; D004247:DNA; D000241:Adenosine