Potentiating effects of pertussis toxin on leukotriene C4 induced formation of inositol phosphate and prostacyclin in human umbilical vein endothelial cells

✍ Scribed by Arnar Geirsson; Haraldur Halldórsson; Kristín Magnúsdóttir; Matthías Kjeld; Gudmundur Thorgeirsson

• Publisher: John Wiley and Sons
• Year: 1998
• Tongue: English
• Weight: 174 KB
• Volume: 177
• Category: Article
• ISSN: 0021-9541
• DOI: 10.1002/(sici)1097-4652(199810)177:1<103::aid-jcp11>3.0.co;2-e

✦ Synopsis

Leukotriene C 4 is an arachidonic acid metabolite and an important mediator of inflammation and anaphylaxis that is known to induce production of prostacyclin in endothelial cells. The goal of this study was to examine the signal transduction mechanisms activated by leukotriene C 4 stimulation. Formation of inositol phosphates was measured to determine the activation of phospholipase C and pertussis toxin was used to explore the role of G-proteins. Additionally, we evaluated the role of protein kinase C in these events, especially whether there was an interaction between pertussis toxin mediated effects and the activity of protein kinase C. Leukotriene C 4 induced a dose-and time-dependent formation of inositol phosphates and prostacyclin. The response to leukotriene C 4 was greater than the response to leukotriene D 4 even after treatment with L-serine borate complex, suggesting the presence of a specific leukotriene C 4 receptor. Exposure to pertussis toxin potentiated, time-dependently, the leukotriene C 4 induced formation of inositol phosphates and prostacyclin through a mechanism which was altered by manipulation of protein kinase C activity. The exact mechanism is not clear but our results are consistent with a postulated dual mechanism of phospholipase C control, in which leukotriene C 4 induced stimulation is attenuated by a pertussis toxin sensitive G-protein.