Effect of adenosine and adenosine 5'-monophosphate on cell division of cultured mastocytoma P-815 cells.
The growth of mouse mastocytoma P-815 cells in culture (37 degrees, 42 hr) was inhibited by exogenous adenosine (0.2 to 1.0 mM) and more effectively by AMP (0.01 to 0.1 mM), but not by adenine. The inhibited growth (a 25% inhibition by 0.5 mM adenosine and a 80% inhibition by 0.25 mM AMP) was restored to a near control level by the addition of uridine (0.5 mM) to the medium. The pretreatment (37 degrees, 3 hr) of the cells with adenosine or AMP caused a 60% inhibition of incorporation (37 degrees, 2 hr) of [U-14C]aspartate into uracil nucleotides, accumulating 14C-orotate and orotidine. Both dipyridamole, an inhibitor of adenosine uptake, and exogenous adenosine deaminase suppressed the growth inhibition induced by not only adenosine but also AMP. 2-Chloroadenosine, which is resistant to the action of adenosine deaminase, was a more potent growth inhibitor, while 3'AMP and 2'-AMP, which are not hydrolyzed to adenosine by membrane 5'-nucleotidase, were ineffective. Adenosine 5'-sulfate and other 5'-substituted adenosines were also ineffective. These observations indicate that AMP inhibits the growth of mastocytoma P-815 cells as a result of its continuous conversion to adenosine and a constant exposure of the cells to a low concentration of adenosine which readily permeates the cell membrane. In addition, adenosine, AMP and their agarose-linked forms rapidly (37 degrees, 20 min) elevated cellular levels of cAMP. This effect was not suppressed by dipyridamole. Apparently adenosine and AMP also act extracellularly for growth inhibition by regulating cAMP levels.
D000227:Adenine Nucleotides / Q000494:pharmacology; D000241:Adenosine / Q000494:pharmacology*; D000249:Adenosine Monophosphate / Q000494:pharmacology*; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism; D012515:Mast-Cell Sarcoma / Q000188:drug therapy* / Q000378:metabolism; D051379:Mice; D012513:Sarcoma, Experimental / Q000188:drug therapy; D014498:Uracil / Q000494:pharmacology
D000227:Adenine Nucleotides; D000249:Adenosine Monophosphate; D014498:Uracil; D000242:Cyclic AMP; D000241:Adenosine