Effect of adenosine 3',5'-monophosphate on growth and several functions of cultured mastocytoma P-815 cells.
Growth-inhibited mouse mastocytoma P-815 cells at stationary phase contained more histamine, serotonin and adenosine 3',5'-monophosphate (cAMP), and higher activities of histidine decarboxylase and adenylate cyclase than the cells during exponential growth. The elevation of endogenous cAMP levels induced by several growth-inhibiting agents such as N6, O2'-dibutyryl cAMP (Bt2cAMP), prostaglandin E1, AMP and 2-chloroadenosine stimulated several functions characteristic of mastocytoma P-815 cells in culture, elevating the synthesis of histamine and serotonin, the activity of chymotrypsin-like protease, and the incorporation of [35S]sulfate into acidic glycosaminoglycans. 1-Methyl-3-isobutyl-xanthine (MIX), a potent inhibitor of cAMP phosphodiesterase, potentiated stimulatory effect of these agents. The results indicate that cAMP regulates the growth and functions of mastocytoma P-815 cells. [35S]-Sulfated acidic glycosaminoglycans synthesized in cells at stationary phase or in cells treated with Bt2cAMP plus MIX mainly localized in the 3000-10000 x g sedimentable fraction of cell homogenates, and had a molecular weight of 200000 to 400000 based on gel filtration. This acidic glycosaminoglycan was resistant to chondroitinase ABC and the heparin-degrading enzyme present in the 20000 x g sedimentable fraction of the cells, and was identified as a highly sulfated macromolecular heparin based on behaviors on DEAE-cellulose column and on acidic electrophoresis. Cycloheximide suppressed the stimulatory effect of Bt2cAMP on the synthesis of histamine and [35S]-sulfated acidic glycosaminoglycan.
D000241:Adenosine / Q000494:pharmacology; D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism / Q000494:pharmacology*; D006025:Glycosaminoglycans / Q000096:biosynthesis; D006632:Histamine / Q000378:metabolism; D012515:Mast-Cell Sarcoma / Q000188:drug therapy* / Q000378:metabolism; D051379:Mice; D011459:Prostaglandins E, Synthetic / Q000494:pharmacology; D012513:Sarcoma, Experimental / Q000188:drug therapy; D012701:Serotonin / Q000378:metabolism
D006025:Glycosaminoglycans; D011459:Prostaglandins E, Synthetic; D012701:Serotonin; D003994:Bucladesine; D006632:Histamine; D000242:Cyclic AMP; D000241:Adenosine