Stimulation of nerve growth factor mRNA content in C6 glioma cells by a beta-adrenergic receptor and by cyclic AMP.
Authentic beta-nerve growth factor mRNA, approximately 1.35 kb in size, has been detected by Northern blot analysis in C6 glioma cells. Exposure of the cells to the beta-adrenergic agonist isoproterenol leads to a three- to fourfold increase in NGF mRNA, which reaches a peak by 2 hr. The EC50 for this effect of isoproterenol is approximately 2nM. The effect can be blocked by the beta-blocker propranolol but not by the alpha-blocker phenoxybenzamine. Treatment of the cells with forskolin also increases NGF mRNA three- to fourfold, with a maximal effect by 2 hr. The stimulation of NGF mRNA by maximal concentrations of forskolin and isoproterenol is not additive; similarly, the two drugs have a nonadditive effect on cyclic AMP content. The results suggest that NGF gene transcription can be stimulated via increases in intracellular cyclic AMP and that regulation of NGF production by glial cells may occur via activation of cell-surface neurotransmitter receptors such as the beta-adrenergic receptor.
Schwartz
J P
JP
Clinical Neuroscience Branch, National Institute of Neurological and Communicative Disorders and Stroke, Bethesda, Maryland 20892.
D000818:Animals; D015152:Blotting, Northern; D002460:Cell Line; D005576:Colforsin / Q000494:pharmacology*; D000242:Cyclic AMP / Q000502:physiology*; D005910:Glioma / Q000378:metabolism*; D007545:Isoproterenol / Q000494:pharmacology*; D008970:Molecular Weight; D009414:Nerve Growth Factors / Q000235:genetics*; D009693:Nucleic Acid Hybridization; D010643:Phenoxybenzamine / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics* / Q000302:isolation & purification; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000502:physiology*
D009414:Nerve Growth Factors; D012333:RNA, Messenger; D011943:Receptors, Adrenergic, beta; D010643:Phenoxybenzamine; D005576:Colforsin; D011433:Propranolol; D000242:Cyclic AMP; D007545:Isoproterenol