Differential effects of phorbol ester and diacylglycerols on inositol phosphate formation in C62B glioma cells.
Application of acetylcholine (ACh) to C62B glioma cells results in a rapid release of inositol phosphates. Since this response is transient, we evaluated the possible role of protein kinase C (PKC) in its desensitization. Pretreatment with 100 nM phorbol 12,13-dibutyrate (PDBu) significantly inhibited ACh-induced accumulation of [3H]inositol mono-, bis-, and trisphosphates. However, interpretation of this result as proof of PKC involvement was complicated by the failure of 1,2-dioctanoylglycerol, 1,2-didecanoylglycerol, or 1-oleoyl-2-acetylglycerol pretreatments to mimic the phorbol ester effect. Further evidence against PKC involvement was obtained using the PKC inhibitor sphingosine; PDBu inhibition of inositol phosphate formation was not reversed by sphingosine pretreatments at concentrations which blocked ACh-stimulated PKC activation of inositol trisphosphate phosphatase activity. These results suggest that there may be phorbol effects not mediated by PKC.
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D002273:Carcinogens / Q000494:pharmacology*; D002460:Cell Line; D004075:Diglycerides / Q000494:pharmacology*; D005910:Glioma / Q000378:metabolism*; D005989:Glycerides / Q000494:pharmacology*; D007295:Inositol Phosphates / Q000096:biosynthesis*; D007700:Kinetics; D015240:Phorbol 12,13-Dibutyrate; D010703:Phorbol Esters / Q000494:pharmacology*; D011493:Protein Kinase C / Q000378:metabolism; D013403:Sugar Phosphates / Q000096:biosynthesis*
D002273:Carcinogens; D004075:Diglycerides; D005989:Glycerides; D007295:Inositol Phosphates; D010703:Phorbol Esters; D013403:Sugar Phosphates; D015240:Phorbol 12,13-Dibutyrate; D011493:Protein Kinase C; D000109:Acetylcholine