Glucocorticoids modify differentially dopamine- and prostaglandin E1-mediated cyclic AMP formation by the cultured human astrocytoma clone D384.
The effects of steroid hormones on the cyclic AMP responses to stimulation of human astrocytoma cells (D384) by dopamine, prostaglandin E1 (PGE1), and isoprenaline were investigated. Incubation of D384 cells with dexamethasone resulted in a potentiation of the PGE1 and isoprenaline responses and a marked attenuation of the dopamine response. The time courses of the effects of dexamethasone on dopamine and PGE1 responses were similar, requiring long-term (at least 18 h) incubation of cells with the steroid. Concentration-response curves of dexamethasone effects on dopamine and PGE1 responses yielded similar Ka apparent values, suggesting a common mechanism. Cycloheximide, a protein synthesis inhibitor, prevented the effects of dexamethasone. Only steroids with glucocorticoid activity reproduced the dexamethasone effects. Direct stimulation of Gs with 5-guanylylimidodiphosphate and adenylate cyclase with forskolin revealed no significant differences in their activities in dexamethasone-treated and untreated cells. Furthermore, a comparison of the dopamine and PGE1 concentration-response curves obtained from dexamethasone-treated and untreated cells suggested that the affinity of the receptors for their agonists remained unchanged. These results suggest that glucocorticoids may alter protein synthesis and thereby the number of receptors expressed by D384 cells.
Balmforth
A J
AJ
M.R.C. Blood Pressure Unit, Western Infirmary, Glasgow, Scotland.
Yasunari
K
K
Vaughan
P F
PF
Ball
S G
SG
D000262:Adenylyl Cyclases / Q000378:metabolism; D000527:Alprostadil / Q000494:pharmacology*; D001254:Astrocytoma / Q000378:metabolism*; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000096:biosynthesis*; D003513:Cycloheximide / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D004298:Dopamine / Q000494:pharmacology*; D019204:GTP-Binding Proteins / Q000378:metabolism; D005938:Glucocorticoids / Q000494:pharmacology*; D006165:Guanylyl Imidodiphosphate / Q000494:pharmacology; D006801:Humans; D007545:Isoproterenol / Q000494:pharmacology; D007700:Kinetics; D014176:Protein Biosynthesis; D014407:Tumor Cells, Cultured
D005938:Glucocorticoids; D005576:Colforsin; D006165:Guanylyl Imidodiphosphate; D003907:Dexamethasone; D003513:Cycloheximide; D000242:Cyclic AMP; D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases; D000527:Alprostadil; D007545:Isoproterenol; D004298:Dopamine