Glucocorticoids inhibit the liberation of arachidonate but not the rapid production of phospholipase C-dependent metabolites in acetylcholine-stimulated C62B glioma cells.
We have previously demonstrated that if C62B glioma cells are prelabeled with [1-14C]arachidonate, cholinergic stimulation results in liberation of radioactive arachidonate and accumulation of radioactive phosphatidate. Cells prelabeled with [2-3H]inositol and stimulated with acetylcholine in the presence of 25 mM LiCl accumulate glycerophosphoinositol and inositol phosphates. The acetylcholine-stimulated accumulation of these products is indicative of activation of both phospholipases A2 and C. When prelabeled cells are pretreated overnight with dexamethasone prior to acetylcholine stimulation, there is preferential inhibition of those products dependent upon phospholipase A2 activity (arachidonate and glycerophosphoinositol accumulation are inhibited 77 and 63%, respectively). During the same time period when phospholipase A2-dependent products are accumulating, there is little effect on the production of phospholipase C-dependent products (acetylcholine-stimulated accumulation of phosphatidate or of inositol phosphates was inhibited by less than 10%). Treatment of C62B cells with two other glucocorticoids, betamethasone and cortisone, produced results similar to those of dexamethasone as did treatment with quinacrine, a phospholipase A2-selective inhibitor. Pretreatment of C62B cells with the mineralocorticoid, aldosterone, did not alter acetylcholine-stimulated response. These results suggest that glucocorticoid treatment results in a preferential inhibition of phospholipase A2 with little effect on the generation of phospholipase C products.
D000109:Acetylcholine / Q000494:pharmacology*; D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism*; D002460:Cell Line; D002478:Cells, Cultured; D003907:Dexamethasone / Q000494:pharmacology; D005910:Glioma / Q000378:metabolism*; D005938:Glucocorticoids / Q000494:pharmacology*; D050356:Lipid Metabolism; D010712:Phosphatidic Acids / Q000378:metabolism; D011796:Quinacrine / Q000494:pharmacology; D010738:Type C Phospholipases / Q000378:metabolism*
D001095:Arachidonic Acids; D005938:Glucocorticoids; D010712:Phosphatidic Acids; D016718:Arachidonic Acid; D003907:Dexamethasone; D010738:Type C Phospholipases; D011796:Quinacrine; D000109:Acetylcholine