Effects of nitrendipine, dotarizine and diltiazem on intracellular calcium in cultured bovine aortic endothelial cells

We have investigated the effects of hypotonic stress on intracellular calcium concentration ([Ca2+]i) in bovine aortic endothelial cells. Reducing extracellular osmolarity by 5% to 40% elicited a steep Ca2+ transient both in normal Krebs and Ca2+-free solutions. The hypotonic stress-induced Ca2+ transient was inhibited by phospholipase C inhibitors (neomycin and U-73122), a P2-receptor antagonist (suramin), and an ATP-hydrolyzing enzyme (apyrase), suggesting that the hypotonic stress-induced Ca2+ transient is mediated by ATP. A luciferin-luciferase assay confirmed that 40% hypotonic stress released 91.0 amol/cell of ATP in 10 min. When the hypotonic stress-induced fast Ca2+ transient was inhibited by neomycin, suramin, or apyrase, a gradual [Ca2+]i increase was observed instead. This hypotonic stress-induced gradual [Ca2+]iincrease was inhibited by a phospholipase A2 inhibitor, 4-bromophenacyl bromide. Furthermore, exogenously applied arachidonic acid induced a gradual [Ca2+]i increase with an ED50 of 13.3 μM. These observations indicate that hypotonic stress induces a dual Ca2+ response in bovine aortic endothelial cells, i.e., an ATP-mediated fast Ca2+transient and an arachidonic acid-mediated gradual Ca2+increase, the former being the predominant response in normal conditions.

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Intracellular calcium ‘signatures’ evoked by different agonists in isolated bovine aortic endothelial cells

Cell Calcium ◽

10.1016/0143-4160(92)90011-g ◽

1992 ◽

Vol 13 (4) ◽

pp. 227-233 ◽

Cited By ~ 15

Author(s):

M. Lynch ◽

J.I. Gillespie ◽

J.R. Greenwell ◽

C. Johnson

Keyword(s):

Endothelial Cells ◽

Intracellular Calcium ◽

Aortic Endothelial Cells ◽

Bovine Aortic Endothelial Cells ◽

Aortic Endothelial

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Tunicamycin increases intracellular calcium levels in bovine aortic endothelial cells

AJP Cell Physiology ◽

10.1152/ajpcell.1997.273.4.c1298 ◽

1997 ◽

Vol 273 (4) ◽

pp. C1298-C1305 ◽

Cited By ~ 24

Author(s):

Barbara J. Buckley ◽

A. R. Whorton

Keyword(s):

Nitric Oxide ◽

Endothelial Cells ◽

Intracellular Calcium ◽

Inositol Phosphates ◽

Protein Glycosylation ◽

Aortic Endothelial Cells ◽

Bovine Aortic Endothelial Cells ◽

Intracellular Ca ◽

Oxide Synthase ◽

Aortic Endothelial

Tunicamycin is a nucleoside antibiotic that inhibits protein glycosylation and palmitoylation. The therapeutic use of tunicamycin is limited in animals because of its toxic effects, particularly in cerebral vasculature. Tunicamycin decreases palmitoylation of the endothelial isoform of nitric oxide synthase, stimulates nitric oxide synthesis, and increases the concentration of intracellular calcium ([Ca2+]i) in bovine aortic endothelial cells (B. J. Buckley and A. R. Whorton. FASEB J. 11: A110, 1997). In the present study, we investigated the mechanism by which tunicamycin alters [Ca2+]iusing the Ca2+-sensitive dye fura 2. We found that tunicamycin increased [Ca2+]iwithout increasing levels of inositol phosphates. When cells were incubated in the absence of extracellular Ca2+, [Ca2+]irapidly rose in response to tunicamycin, although a full response was not achieved. The pool of intracellular Ca2+ mobilized by tunicamycin overlapped with that mobilized by thapsigargin. Extracellular nickel blocked a full response to tunicamycin when cells were incubated in the presence of extracellular Ca2+. The effects of tunicamycin on [Ca2+]iwere partially reversed by washing out the drug, and the remainder of the response was inhibited by removing extracellular Ca2+. These results indicate that tunicamycin mobilizes Ca2+ from intracellular stores in a manner independent of phospholipase C activation and increases the influx of Ca2+ across the plasma membrane.

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Effects of Dipyrone on Prostaglandin Production by Human Platelets and Cultured Bovine Aortic Endothelial Cells

Thrombosis and Haemostasis ◽

10.1055/s-0038-1657338 ◽

1983 ◽

Vol 49 (02) ◽

pp. 132-137 ◽

Cited By ~ 16

Author(s):

A Eldor ◽

G Polliack ◽

I Vlodavsky ◽

M Levy

Keyword(s):

Endothelial Cells ◽

Arachidonic Acid ◽

Competitive Inhibition ◽

Inhibitory Effect ◽

Human Platelets ◽

Ionophore A23187 ◽

Aortic Endothelial Cells ◽

Bovine Aortic Endothelial Cells ◽

Aortic Endothelial

SummaryDipyrone and its metabolites 4-methylaminoantipyrine, 4-aminoantipyrine, 4-acetylaminoantipyrine and 4-formylaminoan- tipyrine inhibited the formation of thromboxane A2 (TXA2) during in vitro platelet aggregation induced by ADP, epinephrine, collagen, ionophore A23187 and arachidonic acid. Inhibition occurred after a short incubation (30–40 sec) and depended on the concentration of the drug or its metabolites and the aggregating agents. The minimal inhibitory concentration of dipyrone needed to completely block aggregation varied between individual donors, and related directly to the inherent capacity of their platelets to synthesize TXA2.Incubation of dipyrone with cultured bovine aortic endothelial cells resulted in a time and dose dependent inhibition of the release of prostacyclin (PGI2) into the culture medium. However, inhibition was abolished when the drug was removed from the culture, or when the cells were stimulated to produce PGI2 with either arachidonic acid or ionophore A23187.These results indicate that dipyrone exerts its inhibitory effect on prostaglandins synthesis by platelets or endothelial cells through a competitive inhibition of the cyclooxygenase system.

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