Effect of secretagogues on chromogranin A synthesis in bovine cultured chromaffin cells. Possible regulation by protein kinase C.
Chromogranin A is a major component of storage granules in many different secretory cell types. After [35S]methionine labelling of proteins from cultured bovine chromaffin cells, chromogranin A was immunoprecipitated with specific antibodies, and the radioactivity incorporated into chromogranin A was determined and used as an index of its synthesis rate. Depolarization of cells with nicotine or high K+ evoked a Ca2+-dependent increase in chromogranin A synthesis, whereas muscarine, which does not evoke significant Ca2+ influx from bovine chromaffin cells, had no effect on chromogranin A synthesis. Forskolin, an activator of adenylate cyclase, affected neither the basal nor the nicotine-stimulated rate of chromogranin A synthesis. In contrast, 12-O-tetradecanoylphorbol 13-acetate (TPA), an activator of protein kinase C, significantly enhanced the incorporation of radioactivity into chromogranin A. Sphingosine, an inhibitor of protein kinase C, abolished both nicotine-stimulated and TPA-induced chromogranin A synthesis. In addition, long-term treatment of chromaffin cells with TPA decreased protein kinase C activity and inhibited the nicotine-stimulated chromogranin A synthesis. These results suggest that protein kinase C may play an important role in the control of chromogranin A synthesis.
Groupe de Neurobiologie Structurale & Fonctionnelle, Unité INSERM U-44, Strasbourg, France.
J P
JP
Simon
M F
MF
Bader
D
D
Aunis
D000262:Adenylyl Cyclases / Q000502:physiology; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002417:Cattle; D002478:Cells, Cultured; D002838:Chromaffin System / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D053379:Chromogranin A; D002864:Chromogranins / Q000096:biosynthesis*; D009116:Muscarine / Q000494:pharmacology; D009419:Nerve Tissue Proteins / Q000096:biosynthesis*; D009538:Nicotine / Q000494:pharmacology*; D011188:Potassium / Q000494:pharmacology*; D011493:Protein Kinase C / Q000502:physiology*; D013755:Tetradecanoylphorbol Acetate
D053379:Chromogranin A; D002864:Chromogranins; D009419:Nerve Tissue Proteins; D009538:Nicotine; D009116:Muscarine; D011493:Protein Kinase C; D000262:Adenylyl Cyclases; D013755:Tetradecanoylphorbol Acetate; D011188:Potassium; D002118:Calcium