Cell cycle specific fluctuations of adenosine 3',5' -monophosphate and prostaglandin binding in synchronized mastocytoma P-815 cells.

Endogenous adenosine 3',5' -monophosphate (cAMP) levels in mastocytoma P-815 cells, synchronized either at the G1/S transition by amethopterin- or double thymidine-block or in mitosis by colcemid block, were highest during late S and early G2 phases and lowest during mitosis. These cell cycle-dependent changes in cAMP levels were largely accounted for by changes in adenylate cyclase and phosphodiesterase activities. Similar fluctuations occurred simultaneously with specific prostaglandin E1 (PGE1) binding, histidine decarboxylase activity, histamine content, and [35S]SO-2(4) incorporation into glycosaminoglycans of the cells. In addition, endogenous levels of the E group of prostaglandins (PGEs) and "14C]carachiodonic acid incorporations into PGE, phosphatidylcholine and phosphatidylinositol also exhibited fluctuation patterns similar to that of cAMP levels. Since cAMP levels still fluctuated in a serum-depleted medium where DNA synthesis and cell division were inhibited, endogeneous levels of prostaglandin and cAMP appeared not to be regulated solely by serum factor(s). Exposure of cells at G1/S transition to 1-methyl-3-isobutylxanthine (MIX) resulted in 10-fold elevation of cAMP levels throughout the cell cycle without affecting DNA synthesis. On the other hand, PGE1 and/or MIX added at late S phase elevated cAMP levels, prolonged C2 phase and retarded the cell division, but these agents added at the beginning of mitosis elevated cAMP levels without affecting the cell division. These results suggest that prostaglandin newly synthesized by the increased metabolism of phospholipids promote the cAMP synthesis via their binding to the receptors and thereby control the division and phenotypic expression of mastocytoma P-815 cells.