Phorbol 12-myristate 13-acetate inhibition of leukotriene D"4-induced signal transduction was rapidly reversed by staurosporine

Activation of leukotriene D"4 receptors results in phospholipase C-mediated breakdown of phosphatidylinositol and increases in intracellular Ca^2^+ in U-937 cells. Treatment (10 min) with phorbol 12-myristate 13-acetate blocked leukotriene D"4-induced phosphatidylinositol metabolism and Ca^2^+ mobil... Ausführliche Beschreibung

1. Person: Winkler, J.D.
Weitere Personen: Sarau, H.M.; Foley, J.J.; Crooke, S.T.
Quelle: in Biochemical and Biophysical Research Communications Vol. 157, No. 2 (1988), p. 521-529
Weitere Artikel
Format: Online-Artikel
Genre: [abr] G protein; guanine nucleotide-binding protein, [abr] IP; inositolpolyphosphates, [abr] LTD"4; leukotriene D"4, [abr] PI; phosphatidylinositol, [abr] PKC; protein kinase C, [abr] PLC; phospholipase C, [abr] PMA; phorbol 12-myristate 13-acetate
Sprache: English
Veröffentlicht: 1988
Beschreibung: Online-Ressource
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Anmerkung: Copyright: Copyright (c) 2006 Elsevier Inc.
Zusammenfassung: Activation of leukotriene D"4 receptors results in phospholipase C-mediated breakdown of phosphatidylinositol and increases in intracellular Ca^2^+ in U-937 cells. Treatment (10 min) with phorbol 12-myristate 13-acetate blocked leukotriene D"4-induced phosphatidylinositol metabolism and Ca^2^+ mobilization (IC"5"0 = 0.2 nM). Treatment with 10 nM phorbol 12-myristate 13-acetate produced blockade which was complete within 1 min and no recovery was observed over 7 days. Addition of the protein kinase C inhibitor staurosporine (100 nM) to U-937 cells pretreated with phorbol 12-myristate 13-acetate for 5 min or 24 hr resulted in a rapid reappearance of leukotriene D"4-induced Ca^2^+ mobilization. Half of the response recovered within 2 min, with complete recovery in 20 min. Staurosporine produced a concentration-related recovery of signal transduction, with an EC"5"0 of 30 nM. These data describe cells which have a novel response to phorbol 12-myristate 13-acetate in that the inhibition of leukotriene D"4 signal transduction is persistent and yet rapidly reversed by staurosporine.
ISSN: 0006-291X

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