Modulation of beta-adrenergic response in rat brain astrocytes by serum and hormones.
Purified astrocyte cultures from neonatal rat cerebrum respond to isoproterenol, a beta-adrenergic agonist, with a transient rise in cAMP production. This astroglial property was regulated by serum, a chemically defined medium (serum-free medium plus hydrocortisone, putrescine, prostaglandin F2 alpha, insulin, and fibroblast growth factor) and epidermal growth factor. Compared to astrocytes grown in serum-supplemented medium, astrocytes grown in the chemically defined medium were nonresponsive to isoproterenol stimulation, and this difference did not appear to be due to selection of a subpopulation of cells by either medium. The data suggest that a decreased beta-adrenergic receptor number and an increased degradation of cAMP may account for the reduced response to beta-adrenergic stimulation. The nonresponsive state of astrocytes in the defined medium was reversible when the medium was replaced with serum-supplemented medium. An active substance(s) in serum was responsible for restoring the responsiveness of astrocytes. Each of the five components of the defined medium had little effect by itself; however, together they acted synergistically to desensitize astrocytes to beta-adrenergic stimulation. On the other hand, epidermal growth factor, a potent mitogen for astrocytes, was very competent by itself in reducing the cAMP response of astrocytes to beta-adrenergic stimulation. Thus purified astrocytes grown in the chemically defined medium appear to be a good model for the study of hormonal interactions and of serum factors which may modulate the beta-adrenergic response.
Wu
D K
DK
Morrison
R S
RS
de Vellis
J
J
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000378:metabolism; D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D001921:Brain / Q000502:physiology*; D002462:Cell Membrane / Q000502:physiology; D002478:Cells, Cultured; D003470:Culture Media; D000242:Cyclic AMP / Q000378:metabolism; D015237:Dinoprost; D005346:Fibroblast Growth Factors / Q000494:pharmacology; D006728:Hormones / Q000494:pharmacology*; D006854:Hydrocortisone / Q000494:pharmacology; D007328:Insulin / Q000494:pharmacology; D007545:Isoproterenol / Q000494:pharmacology; D007700:Kinetics; D011460:Prostaglandins F / Q000494:pharmacology; D011700:Putrescine / Q000494:pharmacology; D051381:Rats; D011943:Receptors, Adrenergic, beta / Q000502:physiology*
D003470:Culture Media; D006728:Hormones; D007328:Insulin; D011460:Prostaglandins F; D011943:Receptors, Adrenergic, beta; D005346:Fibroblast Growth Factors; D015237:Dinoprost; D000242:Cyclic AMP; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D007545:Isoproterenol; D015056:1-Methyl-3-isobutylxanthine; D011700:Putrescine; D006854:Hydrocortisone