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Beta-adrenergic receptor regulation, through cyclic AMP, of nerve growth factor expression in rat cortical and
1Clinical Neuroscience Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892.
Abstract:
1. Type 1 astrocytes prepared from 3-day rat cortex and cerebellum express the 1.3-kb nerve growth factor (NGF) mRNA and synthesize and release beta-NGF. 2. Isoproterenol (IP), a beta-adrenergic agonist, stimulates NGF mRNA content in cortical astrocytes; this increase is blocked by the beta-adrenergic antagonist propranolol but not the alpha-antagonist phenoxybenzamine. The EC50 for the effect of IP is 5 nM. 3. IP increases astrocyte cyclic AMP as does forskolin, which directly activates adenylate cyclase and also increases NGF mRNA content. Cerebellar astrocytes contain about one-third as much NGF mRNA, which can also be increased by forskolin and cyclic AMP. 4. These results suggest that CNS astrocytes can serve as a source of NGF and that the NGF gene is one of the class of cyclic AMP regulated genes.