Glucocorticoid treatment reduces prostacyclin synthesis in response to limited stimuli.
Dexamethasone 21-acetate (DMS 21-A) time- and dose-dependently suppressed bradykinin-stimulated prostacyclin synthesis in porcine aortic endothelial cells. The suppression was more prominent in the presence of pertussis toxin, which by itself could enhance bradykinin-induced prostacyclin synthesis. The DMS 21-A treatment diminished prostacyclin synthesis also in response to vasopressin. In contrast, it did not affect prostacyclin synthesis in response to arachidonic acid or A23187. Melittin-induced prostacyclin synthesis was reduced only at low doses (1-7 x 10(-7) M). The suppression of bradykinin-induced prostacyclin synthesis by DMS 21-A was completely blocked by cycloheximide. DMS 21-A had no effect on the cellular level of lipocortin I protein, but increased the anti-phospholipase A2 activity in EDTA extracts of the cells. These results suggest that the DMS 21-A treatment induces phospholipase A2 inhibitor protein(s) other than lipocortin I and reduces prostacyclin production in response to limited stimuli.
Fujimoto
M
M
Shionogi Research Laboratories, Shionogi & Co., Ltd., Osaka, Japan.
Sakata
T
T
Tsuruta
Y
Y
Iwagami
S
S
Teraoka
H
H
D000818:Animals; D017302:Annexins; D001920:Bradykinin / Q000494:pharmacology; D000001:Calcimycin / Q000494:pharmacology; D002135:Calcium-Binding Proteins / Q000096:biosynthesis; D002478:Cells, Cultured; D003907:Dexamethasone / Q000031:analogs & derivatives* / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D011464:Epoprostenol / Q000096:biosynthesis*; D008555:Melitten / Q000494:pharmacology; D037342:Pertussis Toxin; D010741:Phospholipases A / Q000037:antagonists & inhibitors; D054467:Phospholipases A2; D014667:Vasopressins / Q000494:pharmacology; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D017302:Annexins; D002135:Calcium-Binding Proteins; D010566:Virulence Factors, Bordetella; D014667:Vasopressins; D008555:Melitten; D000001:Calcimycin; D003907:Dexamethasone; D011464:Epoprostenol; C018038:dexamethasone acetate; D037342:Pertussis Toxin; D010741:Phospholipases A; D054467:Phospholipases A2; D001920:Bradykinin