title: Phorbol esters inhibit the synthesis of acetylcholine receptors in cultured muscle cells.
abstract: The acetylcholine receptor (AChR) synthesis, insertion and degradation rates are regulated by numerous intracellular and extracellular agents. Recent studies have shown that Ca2+ and Ca2+ ionophores have a profound regulatory effect on the appearance of AChR clusters and AChR synthesis. These regulatory effects may be mediated through the activation of calcium and phospholipid-dependent protein kinases by agents such as phorbol esters. In this study, we have utilized 4-beta-phorbol-12-myristate-13-acetate (PMA) in order to determine whether the activation of protein kinase C exerts a regulatory effect on the expression of AChRs in cultured chick myotubes. Our results show that 4-beta-phorbol-12-myristate-13-acetate decreased intracellular AChRs and suppressed AChR synthesis without affecting the turnover rate. Control and PMA treated cells labeled with [35S] methionine and immunoprecipitated with a monoclonal antibody to the alpha subunit of AChRs (mAb35) revealed a significant decrease in radioactivity precipitated after exposure to PMA. Polyacrylamide gel electrophoresis revealed no major changes in protein patterns, or in newly synthesized proteins as determined by [35S] methionine incorporation and autoradiography. Other enzymes important in muscle metabolism were not affected by PMA treatment. Our results indicate that activation of protein kinase C results in the suppression of AChRs synthesis and dispersal of AChR clusters.
authors.affiliation: Department of Neurology, Baylor College of Medicine, Houston, TX 77030.
authors.forename: S
authors.initials: S
authors.lastname: Bursztajn
authors.forename: L W
authors.initials: LW
authors.lastname: Schneider
authors.forename: Y J
authors.initials: YJ
authors.lastname: Jong
authors.forename: S A
authors.initials: SA
authors.lastname: Berman
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D002642:Chick Embryo; D003864:Depression, Chemical; D009132:Muscles / Q000166:cytology* / Q000378:metabolism / Q000648:ultrastructure; D010703:Phorbol Esters / Q000494:pharmacology*; D011950:Receptors, Cholinergic / Q000096:biosynthesis* / Q000187:drug effects; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
chemical_list: D010703:Phorbol Esters; D011950:Receptors, Cholinergic; D013755:Tetradecanoylphorbol Acetate