A novel inhibitory role for glucocorticoids in the secretion of angiotensinogen by C6 glioma cells.
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/10(6) 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(-6) M) reduced the rate of Ao secretion to 1.82 +/- 0.28 ng of Ao/10(6) cells/24 h. By comparison, the basal secretion rate for rat H4 hepatoma cells was 142.4 +/- 10.0 ng of Ao/10(6) cells/24 h, and this increased fourfold (572.4 +/- 173.1 ng/10(6) cells/24 h) in the presence of 10(-6) M 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/10(6) cells/24 h, respectively, and by the beta-adrenergic agonist isoprenaline, which stimulates cyclic AMP production.(ABSTRACT TRUNCATED AT 250 WORDS)
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Department of Physiology and Pharmacology, University of Queensland, Brisbane, Australia.
Thomas
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D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000527:Alprostadil / Q000494:pharmacology; D000808:Angiotensinogen / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D000818:Animals; D003994:Bucladesine / Q000008:administration & dosage / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology*; D015237:Dinoprost / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005910:Glioma / Q000378:metabolism*; D007545:Isoproterenol / Q000008:administration & dosage / Q000494:pharmacology; D008114:Liver Neoplasms, Experimental / Q000378:metabolism; D015735:Mifepristone / Q000494:pharmacology; D051381:Rats; D014407:Tumor Cells, Cultured
D000808:Angiotensinogen; D015735:Mifepristone; D003994:Bucladesine; D003907:Dexamethasone; D015237:Dinoprost; D000242:Cyclic AMP; D000527:Alprostadil; D007545:Isoproterenol; D015056:1-Methyl-3-isobutylxanthine