title: Phospholipase D regulates calcium oscillation frequency and nuclear factor-kappaB activity in histamine- stimulated human endothelial cells.
abstract: Histamine stimulates [Ca(2+)](i) oscillations in human aortic endothelial cells (HAEC), the frequency of which regulates the activity of nuclear factor-kappaB (NF-kappaB). This study was performed to determine whether phospholipase D (PLD) is involved in this signaling pathway. At a concentration of 1 microM, which stimulates [Ca(2+)](i) oscillations in this cell type, histamine initiated a twofold increase in [(32)P]phosphatidybutanol (PBt), an index of PLD activity as early as 5 min after stimulation. During established [Ca(2+)](i) oscillations induced by 1 microM histamine, 0.3% n-butanol, which "functionally" redirects phosphatidic acid formed by PLD to PBt, decreased [Ca(2+)](i) oscillation frequency by approximately 50% and produced a similar reduction in NF-kappaB activity. In the presence of the inositol 1,4,5-trisphosphate receptor blocker xestospongin C, which itself decreases the frequency of histamine-stimulated [Ca(2+)](i) oscillations, n-butanol produced a further decrease in oscillation frequency that was not associated with an additional reduction in NF-kappaB activity. This study shows that activation of PLD by histamine regulates [Ca(2+)](i) oscillation frequency and NF-kappaB activity in HAEC.
authors.affiliation: Department of Medicine, Johns Hopkins Bayview Medical Center, Baltimore, Maryland 21224-2780, USA. quinghuaa@welch.jhmi.edu
authors.forename: Qinghua
authors.initials: Q
authors.lastname: Hu
authors.forename: Viswanathan
authors.initials: V
authors.lastname: Natarajan
authors.forename: Roy C
authors.initials: RC
authors.lastname: Ziegelstein
mesh_terms: D020001:1-Butanol / Q000494:pharmacology; D000440:Butanols / Q000494:pharmacology; D015220:Calcium Channels; D020013:Calcium Signaling / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006632:Histamine / Q000494:pharmacology*; D006801:Humans; D053496:Inositol 1,4,5-Trisphosphate Receptors; D007700:Kinetics; D047028:Macrocyclic Compounds; D016328:NF-kappa B / Q000378:metabolism*; D010080:Oxazoles / Q000494:pharmacology; D010739:Phospholipase D / Q000037:antagonists & inhibitors / Q000378:metabolism*; D018160:Receptors, Cytoplasmic and Nuclear / Q000037:antagonists & inhibitors
chemical_list: D000440:Butanols; D015220:Calcium Channels; D004791:Enzyme Inhibitors; C506926:ITPR1 protein, human; D053496:Inositol 1,4,5-Trisphosphate Receptors; D047028:Macrocyclic Compounds; D016328:NF-kappa B; D010080:Oxazoles; D018160:Receptors, Cytoplasmic and Nuclear; C108644:xestospongin A; C043958:2-butanol; D006632:Histamine; D020001:1-Butanol; D010739:Phospholipase D