Interaction between prostacyclin and cortisol in fetal lung cells: effects on cAMP production.
Glucocorticoids secreted by the fetal adrenal, or administered for therapeutic reasons, stimulate fetal lung maturation in the human and other species. Prostacyclin, produced within the lung may be another agent with maturational effects. In this investigation we have demonstrated that glucocorticoids interact with lung cells and increase their response to a prostacyclin analogue (Iloprost, PGIp). This agent stimulates adenylate cyclase activity in fetal lung fibroblasts, fetal lung epithelial cells and in neonatal vascular smooth muscle cells. The cAMP response to PGIp in fibroblasts and epithelial cells occurred in the range 3nM-1 microM. When fibroblasts were pretreated with cortisol before PGIp, cAMP was increased 2-3 fold (p less than 0.01). There was a similar increase in cAMP after cortisol pretreatment in response to PGIp by fetal lung epithelial cells, but not with smooth muscle cells. The action of cortisol was blocked by an inhibitor of RNA synthesis (Actinomycin D) but not by an inhibitor of DNA synthesis (5-fluorodeoxy-uridine). Additional experiments with cholera and pertussis toxins, and with forskolin suggest that cortisol principally increases the quantity or activity of the adenylate cyclase sub-unit in fetal lung fibroblasts and, in doing so, increases the cAMP response to PGIp.
Skinner
S J
SJ
Department of Paediatrics and Surgery, School of Medicine, University of Auckland, New Zealand.
Somervell
C E
CE
Lowe
C
C
D037361:Adenylate Cyclase Toxin; D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D001011:Aorta / Q000166:cytology; D002417:Cattle; D002478:Cells, Cultured; D002772:Cholera Toxin / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism*; D015232:Dinoprostone / Q000494:pharmacology; D004847:Epithelial Cells; D004848:Epithelium / Q000187:drug effects; D005347:Fibroblasts / Q000187:drug effects; D006854:Hydrocortisone / Q000494:pharmacology*; D016285:Iloprost / Q000494:pharmacology*; D008168:Lung / Q000166:cytology* / Q000196:embryology / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism; D012313:RNA / Q000096:biosynthesis; D051381:Rats; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D037361:Adenylate Cyclase Toxin; D010566:Virulence Factors, Bordetella; D005576:Colforsin; D012313:RNA; D002772:Cholera Toxin; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; D016285:Iloprost; D015232:Dinoprostone; D006854:Hydrocortisone