Modulation of cyclic AMP accumulation in glial cells by exogenous phospholipase C.
Pretreatment of 1321N1 human astrocytoma cells with exogenously added bacterial phospholipase C (PLC) induced an increase in subsequent stimulation of cyclic AMP accumulation by the beta-adrenergic receptor agonist isoproterenol and by the direct adenylyl cyclase activator forskolin, a phenomenon referred to as sensitization. The direct protein kinase C activator phorbol 12-myristate 13-acetate (PMA) induced a similar sensitization. In contrast, in C62B rat glioma cells both PLC and PMA induced a decrease in subsequent cyclic AMP accumulation stimulated by isoproterenol and little or no change in stimulation by forskolin. Although the effects of PMA were completely abolished by pretreating cells overnight with PMA to down-regulate protein kinase C activity, the effects of PLC were inhibited only partially or not inhibited. Pertussis toxin pretreatment did not inhibit the sensitization induced by PLC, whereas sensitization induced by lysophosphatidic acid (previously shown to involve pertussis toxin-sensitive GTP binding proteins) was completely inhibited. Further studies of these phenomena may reveal novel pathways for regulation of the cyclic AMP signalling pathway.
Hoffman
J
J
Department of Pharmacology, University of Nebraska Medical Center, Omaha 68198-6260, USA.
Whittle
S
S
Toews
M
M
D037361:Adenylate Cyclase Toxin; D001254:Astrocytoma / Q000378:metabolism; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism*; D015536:Down-Regulation; D005910:Glioma / Q000378:metabolism; D006801:Humans; D007545:Isoproterenol / Q000494:pharmacology; D008246:Lysophospholipids / Q000494:pharmacology; D009457:Neuroglia / Q000187:drug effects / Q000378:metabolism*; D037342:Pertussis Toxin; D011493:Protein Kinase C / Q000378:metabolism; D015398:Signal Transduction; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D010738:Type C Phospholipases / Q000494:pharmacology*; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D037361:Adenylate Cyclase Toxin; D008246:Lysophospholipids; D010566:Virulence Factors, Bordetella; D005576:Colforsin; D000242:Cyclic AMP; D037342:Pertussis Toxin; D011493:Protein Kinase C; D010738:Type C Phospholipases; D007545:Isoproterenol; D013755:Tetradecanoylphorbol Acetate