Modulation of beta‐adrenergic response in rat brain astrocytes by serum and hormones

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Abstract
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 F2α, 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 nonresponsiveto 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.