EFFECTS OF THYMELEATOXIN AND 12-DEOXYPHORBOL-13-PHENYLACETATE-20-ACETATE ON THE STIMULATED RELEASE OF CHOLINE METABOLITES FROM C6 GLIOMA-CELLS

At 100nM both thymeleatoxin (TX) and 12-0-tetradecanoylphorbol-13-acet ate (TPA) maximally stimulated the release of choline metabolites from C6 glioma cells to the external medium by 2.5 to 3 times over basal: for 12-deoxyphorbol-13-phenylacetate-20-acetate (DOPPA) at 100nM the i ncrease was only 1.8 times over basal. At DOPPA concentrations between 500nM and 1 mu M choline metabolite release was the same as for TPA o r TX at 100nM. Neither TPA nor TX stimulated choline metabolite releas e from C6 cells chronically treated with 500nM DOPPA to down-regulate protein kinase C (PKC). Since DOPPA activates only PKC beta(1) in vitr o while TX and TPA activate cPKC and all subspecies respectively (Ryve s et al., FEBS Lett. 288 (1991) 5) our results suggest that PKC beta(1 ) may activate the phospholipase D responsible for stimulated choline phospholipid turnover in C6 cells. Chronic treatment of C6 cells with TPA or DOPPA had no effect on the foetal bovine serum-stimulated relea se of choline metabolites indicating that a PkC-independent pathway to choline metabolite release exists in C6 glioma cells.