The influence of phenelzine and tranylcypromine on the release of prostaglandins from the rat mesenteric vascular bed

1988 ◽  
Vol 66 (9) ◽  
pp. 1206-1209 ◽  
Author(s):  
Bassam A. Nassar ◽  
Yung-Sheng Huang ◽  
Alan T. J. McDonald ◽  
Kenneth D. Jenkins ◽  
David F. Horrobin
Keyword(s):  
Arachidonic Acid ◽  
Linolenic Acid ◽  
Inhibitory Effect ◽  
Prostaglandin E ◽  
Low Doses ◽  
Vascular Bed ◽  
Mesenteric Vascular Bed

We investigated the effects of phenelzine and tranylcypromine on the release of prostacyclin, thromboxane A2, prostaglandin E2, and prostaglandin E1 from the isolated perfused rat mesenteric vascular bed. Perfusion of the preparation with phenelzine in concentrations of 15, 45, and 135 μM for 150 min led to attenuated release of all four prostaglandins measured. Inhibition generally occurred with the lowest dose used and was most prominent with the highest concentration. Tranylcypromine also decreased prostaglandin formation. However, low doses were not effective in the suppression of prostacyclin release. Both drugs had an inhibitory effect on production of prostaglandin E1, which is a metabolite of dihomo-γ-linolenic acid, the precursor of arachidonic acid, but this was only shown to be significant with phenelzine. In this work we demonstrate that phenelzine and tranylcypromine have an inhibitory effect on the production of 2-series prostaglandins derived from arachidonic acid, and possibly a similar effect on prostaglandins of the 1-series derived from dihomo-γ-linolenic acid.

11,12-Epoxyeicosatrienoic Acid Attenuates Synthesis of Prostaglandin E2 in Rat Monocytes Stimulated with Lipopolysaccharide

2003 ◽  
Vol 228 (7) ◽  
pp. 786-794 ◽  
Author(s):  
Wieslaw Kozak ◽  
David M. Aronoff ◽  
Olivier Boutaud ◽  
Anna Kozak
Keyword(s):  
Cell Culture ◽  
Arachidonic Acid ◽  
Negative Feedback ◽  
Inhibitory Effect ◽  
Prostaglandin E ◽  
Dependent Manner ◽  
Epoxyeicosatrienoic Acid ◽  
Concentration Dependent Manner ◽  
Cox 2 ◽  
Cytochrome P 450

Cytochrome P-450 monooxygenase (epoxygenase)-derived arachidonic acid (AA) metabolites, including 11,12-epoxyeicosatrienoic acid (11,12-EET), possess anti-inflammatory and antipyretic properties. Prostaglandin E2 (PGE2), a cyclooxygenase (COX)-derived metabolite of AA, is a well-defined mediator of fever and inflammation. We have tested the hypothesis that 11,12-EET attenuates synthesis of PGE2 in monocytes, which are the cells that are indispensable for induction of fever and initiation of inflammation. Monocytes isolated from freshly collected rat blood were stimulated with lipopolysaccharide (LPS; 100 ng/2 × 105 cells) to induce COX-2 and stimulate generation of PGE2. SKF-525A, an inhibitor of epoxygenases, significantly augmented the lipopolysaccharide-provoked synthesis of PGE2 in cell culture in a concentration-dependent manner. It did not affect, however, elevation of the expression of COX-2 protein in monocytes stimulated with LPS. 11,12-EET also did not affect the induction of COX-2 in monocytes incubated with lipopolysaccharide. However, 11,12-EET suppressed, in a concentration-dependent fashion, the generation of PGE2 in incubates. Preincubation of a murine COX-2 preparation for 0–5 min with three concentrations of 11,12-EET (1, 5, and 10 μM) inhibited the oxygenation of [14C]-labeled AA by the enzyme. The inhibitory effect of 11,12-EET on COX-2 was time-and-concentration-dependent, suggesting a mechanism-based inhibition. Based on these data, we conclude that 11,12-EET suppresses generation of PGE2 in monocytes via modulating the activity of COX-2. These data support the hypothesis that epoxygenasederived AA metabolites constitute a negative feedback on the enhanced synthesis of prostaglandins upon inflammation.

The inhibitory effect of celecoxib on mouse hepatoma H22 cell line on the arachidonic acid metabolic pathwayThis paper is one of a selection of papers published in this special issue entitled “Second International Symposium on Recent Advances in Basic, Clinical, and Social Medicine” and has undergone the Journal's usual peer review process.

2010 ◽  
Vol 88 (4) ◽  
pp. 603-609 ◽  
Author(s):  
Zhigang Xu ◽  
Ming Zhang ◽  
Xiaoyan Lv ◽  
Dan Xiang ◽  
Xuewen Zhang ◽  
...  
Keyword(s):  
Arachidonic Acid ◽  
Peer Review Process ◽  
Inhibitory Effect ◽  
Prostaglandin E ◽  
Dependent Manner ◽  
Important Indicator ◽  
Protein Levels ◽  
Mouse Hepatoma ◽  
Cox 2 ◽  
Risk Of Cancer

Celecoxib is a selective inhibitor of cyclooxygenase-2 (COX-2). It may reduce the risk of cancer formation by affecting the metabolism of arachidonic acid (AA), which has been implicated in the development of cancer. Accordingly, this study was designed to determine the effects of celecoxib on the AA pathway in mouse hepatoma H22 cells. Celecoxib was found to inhibit the proliferation of H22 cells in a dose- and time-dependent manner. Low doses (50 and 100 µmol·L–1) of celecoxib caused an increase in the expression of cytosolic phospholipase A2 (cPLA2), but did not affect the expression of COX-2 in terms of the mRNA and protein levels. Surprisingly, the amount of AA was elevated and the level of prostaglandin E2 (PGE2) was unaltered in the culture supernatant. At higher celecoxib doses (200 and 400 µmol·L–1), the mRNA and protein of both COX-2 and cPLA2 were inhibited. The concentration of AA was increased, and PGE2 level was depressed in H22 cells. The ratio of AA to PGE2 was increased in a dose-dependent manner. Our findings suggest that the imbalance between AA and PGE2, characterized by increased AA at a low dosage and decreased PGE2 at a high dosage of celecoxib, was an important indicator of cytotoxicity of celecoxib on H22 cells.

Vascular Actions of Frusemide and Bumetanide on the Rat Superior Mesenteric Vascular Bed: Interactions with Prostaglandins

1976 ◽  
Vol 51 (s3) ◽  
pp. 257s-258s
Author(s):  
D. F. Horrobin ◽  
M. S. Manku ◽  
J. P. Mtabaji
Keyword(s):  
Prostaglandin E2 ◽  
Inhibitory Effect ◽  
Prostaglandin Synthesis ◽  
Inhibitory Effects ◽  
Perfusion Fluid ◽  
Endogenous Prostaglandin ◽  
Vascular Bed ◽  
Mesenteric Vascular Bed

1. The addition of frusemide or bumetanide to perfusion fluid inhibited the response of the isolated mesenteric vascular bed to noradrenaline. 2. Addition of prostaglandin E2 to the perfusion fluid completely restored the response to noradrenaline. 3. Inhibition of prostaglandin secretion by indomethacin with restoration of responses to noradrenaline by the addition of exogenous prostaglandin E2 prevented the inhibitory effect of frusemide or bumetanide on responses to noradrenaline. 4. The inhibitory effects of diuretics on responsiveness to noradrenaline is mediated by blockade of endogenous prostaglandin synthesis.

Characterization of thromboxane receptor blocking effects of SQ 29548 in the feline pulmonary vascular bed

1992 ◽  
Vol 72 (3) ◽  
pp. 1194-1200 ◽  
Author(s):  
T. J. McMahon ◽  
J. S. Hood ◽  
B. D. Nossaman ◽  
A. L. Hyman ◽  
P. J. Kadowitz
Keyword(s):  
Arachidonic Acid ◽  
Blocking Agent ◽  
Low Doses ◽  
Response Curves ◽  
Receptor Blocking ◽  
Vascular Bed ◽  
Vessel Elements ◽  
Txa2 Receptor ◽  
The Right ◽  
Pulmonary Vascular Bed

The effects of SQ 29548, a thromboxane (Tx) A2 receptor blocking agent, on responses to the TxA2 mimic U46619 were investigated in the pulmonary vascular bed of the intact-chest cat under constant-flow conditions. The administration of SQ 29548 in doses of 0.25–1 mg/kg iv reduced vasoconstrictor responses to U-46619; however, responses to prostaglandins (PG) F2 alpha and D2 and to serotonin were also decreased. After administration of SQ 29548 in doses of 0.05–0.1 mg/kg iv, responses to U-46619 and U-44069 were reduced significantly, and the dose-response curves for these TxA2 mimics were shifted to the right in a parallel manner at a time when responses to PGF2 alpha and PGD2 were not altered. The low doses of the TxA2 receptor blocking agent significantly reduced responses to the PG and TxA2 precursor arachidonic acid but were without significant effect on vasoconstrictor responses to serotonin; histamine; norepinephrine; angiotensin II; the major PGD2 metabolite 9 alpha,11 beta-PGF2; BAY K 8644, an agent that enhances calcium entry; and endothelin-1. The present data show that at low doses SQ 29548 selectively blocks TxA2 receptor-mediated responses in a competitive and reversible manner in the pulmonary vascular bed. These data suggest that responses to arachidonic acid are mediated in large part by the formation of TxA2 and provide evidence in support of the hypothesis that a discrete TxA2 receptor unrelated to PGF2 alpha or PGD2 receptors is present in undefined resistance vessel elements in the feline pulmonary vascular bed.

Vascular actions of furosemide and bumetanide on the rat superior mesenteric vascular bed: interactions with prolactin and prostaglandins

1976 ◽  
Vol 54 (3) ◽  
pp. 357-366 ◽  
Author(s):  
J. P. Mtabaji ◽  
M. S. Manku ◽  
D. F. Horrobin
Keyword(s):  
Pressor Response ◽  
Prostaglandin Synthesis ◽  
Prostaglandin E ◽  
Vascular Effects ◽  
Adequate Amount ◽  
Vascular Bed ◽  
Pressor Responses ◽  
Mesenteric Vascular Bed ◽  
Ovine Prolactin

The mesenteric vascular bed of the rat was used to investigate the effects of furosemide, bumetanide, prolactin, aspirin, indomethacin and prostaglandin E2 on the pressor response to norepinephrine. Furosemide, bumetanide and indomethacin could all inhibit the responses to norepinephrine: in each case responsiveness was restored by the addition of prostaglandin E2 to the perfusate. Bumetanide and furosemide both failed to inhibit responsiveness in the presence of an adequate amount (50 pg/ml) of prostaglandin E2. As has been shown previously, ovine prolactin in a concentration of 50 ng/ml enhanced pressor responses to norepinephrine while 500 ng/ml, after an initial potentiation, inhibited responsiveness. Aspirin, furosemide and bumetanide all reversed both the potentiation produced by the lower prolactin concentration and the inhibition produced by the higher one. When taken in conjunction with other evidence these results suggest that the diuretics exert their vascular effects by inhibiting prostaglandin synthesis whereas prolactin acts by stimulating such synthesis.

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

1983 ◽  
Vol 49 (02) ◽  
pp. 132-137 ◽  
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.

Selective Inhibition of Thromboxane Synthetase with Dazoxiben - Basis of Its Inhibitory Effect on Platelet Adhesion

1983 ◽  
Vol 49 (02) ◽  
pp. 096-101 ◽  
Author(s):  
V C Menys ◽  
J A Davies
Keyword(s):  
Arachidonic Acid ◽  
Platelet Adhesion ◽  
Fold Increase ◽  
Selective Inhibition ◽  
Inhibitory Effect ◽  
Selective Inhibitor ◽  
Coated Glass ◽  
Thromboxane Synthetase ◽  
Pre Treatment

SummaryPlatelet adhesion to rabbit aortic subendothelium or collagen-coated glass was quantitated in a rotating probe device by uptake of radio-labelled platelets. Under conditions in which aspirin had no effect, dazoxiben, a selective inhibitor of thromboxane synthetase, reduced platelet adhesion to aortic subendothelium by about 40% but did not affect adhesion to collagen-coated glass. Pre-treatment of aortic segments with 15-HPETE, a selective inhibitor of PGI2-synthetase, abolished the inhibitory effect of dazoxiben on adhesion. Concentrations of 6-oxo-PGFlα in the perfusate were raised in the presence of dazoxiben alone, and following addition of thrombin (10 units/ml) there was a 2-3 fold increase in concentration. Perfusion of damaged aorta with platelets labelled with (14C)-arachidonic acid in the presence of thrombin and dazoxiben resulted in the appearance of (14C)-labelled-6-oxo-PGFiα. Inhibition of thromboxane synthetase limits platelet adhesion probably by promoting vascular synthesis of PGI2 from endoperoxides liberated from adherent platelets, which subsequently promotes detachment of cells from the surface.

Analysis of the Effects of Candesartan in the Mesenteric Vascular Bed of the Cat

Hypertension ◽  
1997 ◽  
Vol 30 (5) ◽  
pp. 1260-1266 ◽  
Author(s):  
Hunter C. Champion ◽  
Philip J. Kadowitz
Keyword(s):  
Vascular Bed ◽  
Mesenteric Vascular Bed

Interaction between cortisol and arachidonic acid on the secretion of LH from ovine pituitary tissue

1991 ◽  
Vol 131 (1) ◽  
pp. 87-94 ◽  
Author(s):  
A. W. Nangalama ◽  
G. P. Moberg
Keyword(s):  
Arachidonic Acid ◽  
Plasma Membrane ◽  
Suppressive Effect ◽  
Inhibitory Effect ◽  
Adrenal Steroids ◽  
Membrane Phospholipids ◽  
Pituitary Tissue ◽  
Receptor Sites ◽  
Lh Release ◽  
Gonadotrophin Releasing Hormone

ABSTRACT In several species, glucocorticoids act directly on the pituitary gonadotroph to suppress the gonadotrophin-releasing hormone (GnRH)-induced secretion of the gonadotrophins, especially LH. A mechanism for this action of these adrenal steroids has not been established, but it appears that the glucocorticoids influence LH release by acting on one or more post-receptor sites. This study investigated whether glucocorticoids disrupt GnRH-induced LH release by altering the liberation of arachidonic acid from plasma membrane phospholipids, a component of GnRH-induced LH release. Using perifused ovine pituitary tissue, it was established that exposure of gonadotrophs to 1–1000 nmol cortisol/l for 4 h or longer significantly reduced GnRH-stimulated LH release with the maximal inhibitory effect being observed after 6 h of exposure to cortisol. This suppressive effect of cortisol could be reversed by administration of arachidonic acid, which in its own right could stimulate LH release from ovine pituitary tissue. Furthermore, the inhibitory effect of cortisol on GnRH-stimulated LH release could be directly correlated with decreased pituitary responsiveness to GnRH-stimulated arachidonic acid liberation, consistent with our hypothesis that glucocorticoids can suppress GnRH-induced secretion of LH by reducing the amount of arachidonic acid available for the exocytotic response of GnRH. Journal of Endocrinology (1991) 131, 87–94

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