Regulation of acetylcholinesterase activity by nerve growth factor. Role of transcription and dissociation from effects on proliferation and neurite outgrowth.
Studies are elaborated on regulation of acetylcholinesterase activity by nerve growth factor (NGF) in cultures of clonal PC12 pheochromocytoma cells. Acetylcholinesterase specific activity in these cultures is maximally and half-maximally increased by NGF concentrations of approximately 1-1.5 and 0.5 nM, respectively. These increases are blocked by antiserum to NGF and are neither mimicked nor significantly altered by epidermal growth factor (1-1000 ng/ml), dexamethasone (10 microM), or dibutyryl cAMP (1 mM). The action of NGF on acetylcholinesterase activity is abolished by low concentrations of the inhibitors of RNA synthesis, camptothecin and actinomycin D. Such findings indicate a transcriptional requirement for this effect of NGF. A series of PC12 variants were employed that in serum-containing medium do not show normal PC12 responses to NGF such as cessation of proliferation and neurite outgrowth. Each of the variants exhibited NGF-dependent increases in acetylcholinesterase specific activity. This suggests that the effects of NGF on regulation of acetylcholinesterase activity can be dissociated from the effects of the factor on neurite outgrowth and proliferation, and that NGF may therefore work via parallel or branching pathways.
D000110:Acetylcholinesterase / Q000378:metabolism*; D000310:Adrenal Gland Neoplasms / Q000201:enzymology*; D000818:Animals; D001369:Axons / Q000502:physiology; D002166:Camptothecin / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D002999:Clone Cells; D003609:Dactinomycin / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D009414:Nerve Growth Factors / Q000494:pharmacology*; D010673:Pheochromocytoma / Q000201:enzymology*; D051381:Rats; D014158:Transcription, Genetic / Q000187:drug effects
D009414:Nerve Growth Factors; D003609:Dactinomycin; D000110:Acetylcholinesterase; D002166:Camptothecin