Beta-adrenergic receptor regulation, through cyclic AMP, of nerve growth factor expression in rat cortical and cerebellar astrocytes.
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.
Schwartz
J P
JP
Clinical Neuroscience Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892.
Mishler
K
K
D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D002531:Cerebellum / Q000166:cytology*; D002540:Cerebral Cortex / Q000166:cytology*; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000502:physiology*; D005786:Gene Expression Regulation; D007545:Isoproterenol / Q000494:pharmacology; D009414:Nerve Growth Factors / Q000096:biosynthesis* / Q000235:genetics; D010643:Phenoxybenzamine / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D011943:Receptors, Adrenergic, beta / Q000502:physiology*; D015290:Second Messenger Systems
D009414:Nerve Growth Factors; D012333:RNA, Messenger; D011943:Receptors, Adrenergic, beta; D010643:Phenoxybenzamine; D005576:Colforsin; D011433:Propranolol; D000242:Cyclic AMP; D007545:Isoproterenol