Leukotriene C: a slow-reacting substance from murine mastocytoma cells.

Murphy, Robert C.; Hammarström, Sven; Samuelsson, Bengt

doi:10.1073/pnas.76.9.4275

Cited by 878 publications

(297 citation statements)

References 22 publications

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“…Recently, however, the use of calcium ionophore A 23187-stimulated mouse mastocytoma cells (4,5) or rat basophilic leukemia cells (6,7) has led to the generation of SRS in sufficient quantity to allow for their chemical characterization. These SRS were identified as metabolites of arachidonic acid (20:4) and named leukotrienes C and D (LTC and LTD).…”

mentioning

confidence: 99%

Dynamics of leukotriene C production by macrophages.

Rouzer¹,

Scott²,

Hamill³

et al. 1980

The Journal of Experimental Medicine

101

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A method for the radiochemical assay of LTC production by mouse peritoneal macrophages in vitro is presented. The method involves labeling macrophages in culture with [5,6,8,9,11,12,14,15-3H]20:4 followed by stimulation of arachidonic acid (20:4) release under the experimental conditions desired. Radiolabeled leukotriene C (LTC) is recovered from the culture medium by extraction and silicic acid chromatography in 40% yield with full retention of biological activity. Because this LTC is radiochemically pure, the quantity of LTC release may be estimated from the amount of radioactivity in the sample. Use of the radioassay to study parameters affecting LTC synthesis by macrophages indicated that the time course of LTC synthesis and its relationship to the dose of a phagocytic stimulus (zymosan) were very similar to those of prostaglandin (PG) release. LTC release was also similar to that of PG in that lower levels of both metabolites were produced by Corynebacterium parvum-elicited macrophages than by resident cells. Finally, LTC release was stimulated in response to a challenge with antigen-antibody complexes, but lower maximal levels were attained than those with zymosan. The data presented here are consistent with the hypothesis that challenge of macrophages with a phagocytic stimulus leads to the release of 20:4 by an inducible phospholipase. Cyclooxygenase and lipoxygenase then compete for the released 20:4, leading to the production of PG, hydroxyeicosatetraenoic acids, and LTC.

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mentioning

confidence: 99%

Dynamics of leukotriene C production by macrophages.

Rouzer¹,

Scott²,

Hamill³

et al. 1980

The Journal of Experimental Medicine

101

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“…When either of these inhibitors was superfused over the trachea at concentrations between 10 j.g/ml to 40 jg/ml for 20 min before and during a histamine dose-response curve, the control histamine dose- (Murphy, Hammarstrom & Samuelsson, 1979) we investigated the action of the SRS-A antagonist, FPL55712 sodium 7-[3-(4-acetyl-3-hydroxy-2-propylphenoxy}2-hydroxypropoxy]-4-oxo-8-propyl-4H-1-benzopyran-2-carboxylate (Augstein, Farmer, Lee, Sheard & Tattersall, 1973) against histamine contractions previously augmented by indomethacin. In two preliminary experiments, FPL55712 at a concentration of 0.5 j.g/ml completely antagonized SRS-Ainduced contractions of the guinea-pig trachea while leaving histamine contractions unchanged.…”

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confidence: 99%

A Possible Role for Lipoxygenase Products as Regulators of Airway Smooth Muscle Reactivity

Adcock

Garland

1980

British J Pharmacology

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The size of guinea-pig isolated tracheal contractions induced by histamine was substantially augmented by pretreatment with the cyclo-oxygenase inhibitor, indomethacin. However, compounds which inhibit both the cyclo-oxygenase and lipoxygenase pathways of arachidonic acid metabolism not only did not augment histamine-induced contractions of the guinea-pig trachea, but also completely reversed the increased reactivity to histamine produced by indomethacin. The SRS-A (slow reacting substance of anaphylaxis) antagonist, FPL55712, and the anti-allergic drug, cromoglycate, had no effect on the augmentation of histamineinduced contractions by indomethacin.

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“…Since free arachidonic acid can be metabolized to a range of potent biologically active products (prostaglandins, thromboxanes, hydroxylated fatty acids : Flower, 1978a; slow-reacting substance: Murphy, Hammarstrom & Samuelsson, 1979), this action of glucocorticoids could well explain, at least in part, their potent anti-inflammatory and anti-allergic properties. The data supporting this hypothesis are largely from in vitro studies, using either isolated tissues, organs, or cultured cells.…”

Section: Introduction Methodsmentioning

confidence: 99%

Inhibition of Arachidonic Acid Release as the Mechanism by Which Glucocorticoids Inhibit Endotoxin‐induced Diarrhoea

Doherty¹

1981

British J Pharmacology

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Dexamethasone blocked endotoxin‐induced diarrhoea in mice, but not that induced by arachidonic acid or prostaglandin E2. Indomethacin blocked endotoxin and arachidonic acid‐induced diarrhoea, but not that induced by prostaglandin E2. Codeine blocked all three forms of diarrhoea. The above data, when considered in relation to literature reports that endotoxin induces prostaglandin synthesis, suggest that dexamethasone blocks diarrhoea by preventing the release of arachidonic acid, the substrate for prostaglandin biosynthesis. The activities of indomethacin and dexamethasone in castor oil diarrhoea support the above conclusion and their inactivity in 5‐hydroxytryptophan‐induced diarrhoea confirms the absence of ‘codeine‐like’ direct effects on the gut. Other glucocorticoids (hydrocortisone, prednisolone) were also able to block endotoxin diarrhoea, but oestradiol, testosterone and progesterone did not. The inhibitory action of dexamethasone on endotoxin diarrhoea could not be blocked by the protein synthesis inhibitor, cycloheximide, nor by the glucocorticoid receptor antagonist, progesterone. Thus, involvement of glucocorticoid receptor‐mediated gene activation could not be demonstrated.

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Leukotriene C: a slow-reacting substance from murine mastocytoma cells.

Cited by 878 publications

References 22 publications

Dynamics of leukotriene C production by macrophages.

Dynamics of leukotriene C production by macrophages.

A Possible Role for Lipoxygenase Products as Regulators of Airway Smooth Muscle Reactivity

Inhibition of Arachidonic Acid Release as the Mechanism by Which Glucocorticoids Inhibit Endotoxin‐induced Diarrhoea

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