Beta adrenergic and prostaglandin receptor activation increases nerve growth factor mRNA content in C6-2B rat...

C6-2B rat astrocytoma cells were used to test whether the increase of cellular nerve growth factor (NGF) content and secretion induced by isoproterenol treatment are associated with an increase in the content of mRNA that encodes NGF (NGF mRNA). Incubation of cells with isoproterenol (10 microM) for different time periods produced an increase of NGF mRNA content (3- to 5-fold over control) reaching maximum levels at 3 hr and lasting up to 24 hr. The isoproterenol effect on NGF mRNA was antagonized by the beta adrenergic receptor antagonist I-propranolol (10 microM) but not by phentolamine (10 microM), an alpha adrenergic receptor antagonist. When C6-2B astrocytoma cells were exposed for a short time to isoproterenol (10 microM; 10 or 20 min) followed by a washout period of 3 hr, the NGF mRNA content was increased by about 2-fold. The increase of NGF mRNA was obtained also with 10 microM prostaglandin E1 and this effect was potentiated by 100 microM of 3-isobutyl-1-methylxanthine. Inasmuch as both isoproterenol and prostaglandin E1 increase cyclic AMP content, one can surmise that cyclic AMP is involved in the stimulation of NGF mRNA accumulation. Whether cyclic AMP directly activates NGF gene transcription or activates an intermediate step, however, cannot be assessed by the present experiments.