EFFECTS OF ADENINE-NUCLEOTIDES ON THE PROLIFERATION OF AORTIC ENDOTHELIAL-CELLS

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 [H-3]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-mu-M and a small one at 100-mu-M; 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. In conclusion, the action of ATP on the proliferation of BAECs is complex: an increase in the fraction of cells synthesizing DNA, no effect on the cell proliferation in the presence of serum, and inhibition of the growth-promoting effect of basic fibroblast growth factor.