Bradykinin-induced release of PGI2 from aortic endothelial cell lines: responses mediated selectively by Ca2+ ions or a staurosporine-sensitive kinase.
1. Bradykinin (100 nM) triggers release of nitric oxide and prostacyclin from both AG07680A and AG04762 bovine cultured aortic endothelial cells. The exposure of these cells to bradykinin is in each case associated with a striking rise in intracellular calcium ion concentration. 2. Exposure of AG07680A cells to 250 nM ionomycin was followed also by a significant release of prostacyclin, whereas 250 nM ionomycin had no capacity to stimulate release of prostacyclin from AG04762 cells. 3. There was a similar concentration-dependent increase in intracellular calcium ion concentration on exposure of AG07680A and AG04762 cells to ionomycin. 4. Exposure of AG04762 cells for 10 min to staurosporine produced a concentration-dependent inhibition (IC50 = 107 +/- 14 nM) in bradykinin-stimulated prostacyclin release. There was no similar inhibitory effect of staurosporine in AG07680A cells. 5. Bradykinin (10 nM) triggered release of nitric oxide from both AG07680A and AG04762 cells, and the effect was not inhibited by 500 nM staurosporine. There was a similar ionomycin-dependent release of nitric oxide from both cell types. 6. These results identify a common pathway for bradykinin-dependent nitric oxide release from both AG07680A and AG04762 cells, involving increases in intracellular calcium ion concentration. In contrast, the bradykinin-dependent release of prostacyclin may involve one of two pathways (involving an increase in intracellular calcium or activation of a staurosporine-sensitive kinase), and the two pathways are selectively exploited in AG07680A and AG04762 cells, respectively.
Parsaee
H
H
Department of Clinical Pharmacology, Royal Postgraduate Medical School, London.
McEwan
J R
JR
MacDermot
J
J
D015121:6-Ketoprostaglandin F1 alpha / Q000494:pharmacology; D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000378:metabolism; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001920:Bradykinin / Q000494:pharmacology*; D002118:Calcium / Q000502:physiology*; D002417:Cattle; D002460:Cell Line; D004730:Endothelium, Vascular / Q000201:enzymology / Q000378:metabolism*; D011464:Epoprostenol / Q000378:metabolism*; D015759:Ionomycin / Q000494:pharmacology; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000494:pharmacology; D010770:Phosphotransferases / Q000037:antagonists & inhibitors / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology; D019311:Staurosporine; D019323:omega-N-Methylarginine
D000470:Alkaloids; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D015759:Ionomycin; D015121:6-Ketoprostaglandin F1 alpha; D001120:Arginine; D011464:Epoprostenol; D010770:Phosphotransferases; D019311:Staurosporine; D001920:Bradykinin; D002118:Calcium