A23187 and protein kinase C activators stimulate phosphatidylinositol metabolism and prostaglandin synthesis in a human lung cancer cell line.
Activation of cell phospholipase, release of arachidonic acid and stimulation of prostaglandin synthesis were studied in a newly described human tumor cell line (Lu-65). In the Lu-65 tumor cell line, the calcium ionophore A23187 (2 microM) caused a 100% increase in the release of 3H-arachidonic acid and a 7-fold increase in the synthesis of prostaglandin E2. 1-oleoyl, -2-acetyl-glycerol (100 microM) increased arachidonate release and prostaglandin E2 synthesis by 100%. A23187 and the protein kinase C activators, 1,2-dioctanoyl-glycerol and 1-oleoyl, -2-acetyl-glycerol, decreased the specific radioactivity of 3H-arachidonate in phosphatidylinositol by 37% and 57%, respectively. The effects of A23187 were blocked in Ca2+-free media or in the presence of the phospholipase A2 inhibitor, p-bromophenacyl bromide, while those of 1-oleoyl, -2-acetyl-glycerol were not. The data provide evidence in a human tumor cell line for calcium/phospholipase A2-dependent and independent pathways for arachidonic acid release, both of which preferentially hydrolyze phosphatidylinositol.
D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism; D000001:Calcimycin / Q000494:pharmacology*; D002118:Calcium / Q000494:pharmacology; D004075:Diglycerides / Q000494:pharmacology; D015232:Dinoprostone / Q000096:biosynthesis*; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism*; D010716:Phosphatidylinositols / Q000378:metabolism*; D010741:Phospholipases A / Q000378:metabolism; D054467:Phospholipases A2; D011493:Protein Kinase C / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D001095:Arachidonic Acids; D004075:Diglycerides; D010716:Phosphatidylinositols; C044295:1,2-dioctanoylglycerol; D016718:Arachidonic Acid; D000001:Calcimycin; C038237:1-oleoyl-2-acetylglycerol; D011493:Protein Kinase C; D010741:Phospholipases A; D054467:Phospholipases A2; D015232:Dinoprostone; D002118:Calcium