ISSN:
1471-4159
Source:
Blackwell Publishing Journal Backfiles 1879-2005
Topics:
Medicine
Notes:
Abstract: Astrocytes have been identified as the primary source of brain angiotensinogen (Ao), but the regulation of the secretion of this protein from astrocytes is poorly defined. In this study, the rat C6 glioma cell line was used as an astrocyte model to investigate the regulation of Ao secretion. C6 cultures secreted Ao at a rate of 4.05 ± 1.52 (mean ± SD) ng of Ao/106 cells/24 h as determined by a direct radioimmunoassay. This rate was not significantly altered by the hormones thyroxine, estradiol, angiotensin II, growth hormone, and prostaglandins or by increased levels of intracellular cyclic AMP. Treatment with the synthetic glucocorticoid dexamethasone (DEX; 10–6M) reduced the rate of Ao secretion to 1.82 ± 0.28 ng of Ao/108 cells/24 h. By comparison, the basal secretion rate for rat H4 hepatoma cells was 142.4 ± 10.0 ng of Ao/106 cells/24 h, and this increased fourfold (572.4 ± 173.1 ng/106 cells/ 24 h) in the presence of 10–6M DEX. Both these inhibitory (C6) and stimulatory (H4) actions of DEX were dose related. The inhibition observed in C6 cells was mimicked by RU28362, a pure glucocorticoid agonist, and reversed by the antagonist RU486, demonstrating that DEX was functioning as a true glucocorticoid. The action of DEX was also antagonized by the cyclic AMP analogue N6,2′-O- dibutyryladenosine 3′:5′-cyclic monophosphate (dBcAMP) (control, DEX, and DEX + dBcAMP, 3.58 ± 0.73, 1.69 ± 0.82, and 4.93 ± 1.88 ng of Ao/106 cells/24 h, respectively, and by the β-adrenergic agonist isoprenaline, which stimulates cyclic AMP production. It was concluded that glucocorticoids inhibit Ao secretion, possibly by interacting with a cyclic AMP-responsive pathway. The inhibition of Ao production by DEX is a novel observation supporting the view that regulation of Ao is tissue specific.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1046/j.1471-4159.1994.62041296.x
