Modulation of the Formation and Release of Bovine SRS-A &lt;i&gt;in vitro&lt;/i&gt; by several Anti-Anaphylactic Drugs

Burka, John F.; Eyre, P.

doi:10.1159/000231461

Cited by 30 publications

(22 citation statements)

References 6 publications

(8 reference statements)

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“…Because indomethacin enhanced the postcapillary leakage to ovalbumin also in mepyramine-treated animals, modulated release of other mediators such as leukotrienes C4, D4, and E4 may have contributed, as indicated by studies in vitro (18,20,22,23). However, neither histamine nor cysteinyl-leukotrienes mediate the leukocyte accumulation and associated leakage of plasma enhanced by indomethacin, a phenomenon predicted to require increased release of chemotactic mediator(s).…”

Section: Resultsmentioning

confidence: 99%

Enhancement of acute allergic inflammation by indomethacin is reversed by prostaglandin E2: apparent correlation with in vivo modulation of mediator release.

Raud

Dahlén

Sydbom

et al. 1988

Proc. Natl. Acad. Sci. U.S.A.

106

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Intravital microscopy and determination of in vivo histamine release revealed that the cyclooxygenase inhibitor indomethacin reduced antigen-induced vasodilation while enhancing plasma extravasation, leukocyte accumulation, and histamine release in cheek pouches of immunized hamsters. Topical application of prostaglandin E2 (PGE2, 30 nM) totally reversed the indomethacin-induced potentiation of the inflammatory reaction to antigen challenge and suppressed both the histamine release and plasma leakage also in the absence of indomethacin. On the other hand, PGE2, which per se caused vasodilation, markedly potentiated the postcapillary leakage of plasma induced by histamine or leukotriene C4, as well as the leukocyte activation and subsequent plasma extravasation evoked by leukotriene B4. Taken together, the data indicate that PGE2 reduced the antigen response by suppression of mediator release from the numerous mast cells present in the cheek pouch. Moreover, the PGE2-sensitive potentiation by indomethacin of the antigen response suggests that endogenous vasodilating prostaglandins (possibly PGE2) predominantly were antiinflammatory.The potent vasodilator prostaglandin E2 (PGE2) is released at sites of inflammation, causes a wheal and flare reaction when injected into skin, and enhances the effects of pain-and edema-producing stimuli (cf. ref. 1). Moreover, nonsteroidal antiinflammatory drugs (NSAIDs) inhibit the fatty acid cyclooxygenase, which catalyzes the initial steps in the biosynthesis of PGE2 from arachidonic acid (cf. ref. 1). Hence, PGE2 is considered to be an inflammatory mediator. Nevertheless, PGE2 and related compounds also exhibit antiinflammatory activities (2-8), and NSAIDs sometimes augment inflammation (9, 10). These conflicting observations complicate understanding of the functional role of PGE2 in inflammation.In the present study, intravital microscopy of the hamster cheek pouch was used to characterize the influence of PGE2 and the prototype of NSAIDs, indomethacin, on microcirculatory dynamics during acute mast cell-dependent inflammation evoked by antigen challenge. Supported also by in vivo measurements of antigen-induced histamine release from the cheek pouch and analysis of the microvascular interactions between exogenous inflammatory mediators and PGE2, we conclude that endogenous cyclooxygenase products predominantly inhibit acute allergic inflammation via local suppression of inflammatory mediator release.MATERIALS AND METHODS Drugs and Chemicals. Leukotrienes B4 and C4 (LTB4, LTC4) were provided by J. Rokach (Merck Frosst Labs, Pointe Claire, PQ) and PGE2 by J. Pike (Upjohn). Arachidonic acid was from Nu Chek Prep. Stock solutions of LTB4, PGE2, and arachidonic acid were stored at -20°C in ethanol, and LTC4 was stored similarly in ethanol/water, 1:1. Concentrations and purity of the icosanoids were checked before use by appropriate methods (UV spectrometry, reverse-phase HPLC, and thin-layer chromatography). Acetylcholine chloride, fluorescein isothiocyanate-conjugated dextr...

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Section: Resultsmentioning

confidence: 99%

Enhancement of acute allergic inflammation by indomethacin is reversed by prostaglandin E2: apparent correlation with in vivo modulation of mediator release.

Raud

Dahlén

Sydbom

et al. 1988

Proc. Natl. Acad. Sci. U.S.A.

106

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“…It has earlier been reported that DECC inhibits responses to histamine and 5-HT (Burka & Eyre, 1974) and the Schultz-Dale reaction (Eyre, 1971). High doses of DECC have been reported to inhibit immunological release of SRS-A (Orange et al, 1968;Burka & Eyre, 1975) and the inhibition of the Schultz-Dale phenomenon by large doses of DECC appears to suggest the formation and release of SRS-A from intestinal tissues but lack of specificity of DECC on a variety of exogenous agonists makes such a conclusion tenuous. Furthermore, antigen-induced release of SRS-A and histamine from chicken lung and intestine in vitro could not be demonstrated (Chand & Eyre, unpublished).…”

Section: Discussionmentioning

confidence: 99%

“…The inhibition of the Schultz-Dale reaction by this compound may be due to the inhibition of formation and release of histamine and SRS-A (Broughton et al, 1974;Burka & Eyre, 1975) by virtue of blocking cyclic 3',5'-adenosine monophosphate phosphodiesterase.…”

Section: Discussionmentioning

confidence: 99%

“…This technique allowed comparisons of responses of 'twin' strips to exogenous agonists and antigen in the presence and absence of antagonists; one strip of each pair always serving as a control (untreated by antagonist) in each experiment (Eyre, 1971). A transverse crop strip was carefully dissected without stretching the tissue (Everett, 1966 (Gaddum, Hameed, Hathway & Stephens, 1955 (Burka & Eyre, 1975 Histamine (1 nm to 0.1 gM) sometimes produced a slight relaxation but as the doses of histamine were increased, only contractile responses were recorded. In general, acetylcholine (ACh) was 100 to 1000 times more active than histamine and 5-hydroxytryptamine (5-HT) on most tissues.…”

Section: Methodsmentioning

confidence: 99%

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The Pharmacology of Anaphylaxis in the Chicken Intestine

Chand

Eyre

1976

British J Pharmacology

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“…Inhibitors of the cyclo-oxygenase pathway of arachidonic acid metabolism enhance immunological SRS-A release from the lungs of man (Walker, 1972), ox (Burka & Eyre, 1975), and guinea-pig (Liebig, Bernauer & Peskar, 1976). Eicosatetraynoic acid (ETA) a cyclo-oxygenase and lipoxygenase inhibitor, does not modify the immunological release of histamine or SRS-A from guinea-pig lung (Engineer, Niederhauser, Piper & Sirois, 1978).…”

Section: Introductionmentioning

confidence: 99%

Effects of Modulators of Arachidonic Acid Metabolism on the Synthesis and Release of Slow‐reacting Substance of Anaphylaxis

Burka

Flower

1979

British J Pharmacology

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Slow‐reacting substance of anaphylaxis (SRS‐A) was released in the peritoneum of passively sensitized rats challenged with ovalbumin and from rat isolated peritoneal cells stimulated with calcium ionophore A23187. Both monocytes (macrophages) and mast cells appear to be involved in the synthesis and release of SRS‐A. The immunological release of SRS‐A in vivo is enhanced by indomethacin and inhibited by dexamethasone, mepacrine, 1‐phenyl‐3‐pyrazolidone (1‐P‐3‐P), and methylimidazole. SRS‐A release induced by A23187 in vitro is inhibited by dexamethasone, indomethacin, 1‐P‐3‐P, eicosatetraynoic acid (ETA) and 15‐hydroperoxy arachidonic acid. The inhibition induced by dexamethasone, indomethacin and 1‐P‐3‐P is reduced by an increase in the calcium concentration from 1 mm to 5 mm, whereas the inhibition induced by ETA is increased. The results suggest that a lipoxygenase is important in the synthesis and release by SRS‐A.

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Modulation of the Formation and Release of Bovine SRS-A <i>in vitro</i> by several Anti-Anaphylactic Drugs

Cited by 30 publications

References 6 publications

Enhancement of acute allergic inflammation by indomethacin is reversed by prostaglandin E2: apparent correlation with in vivo modulation of mediator release.

Enhancement of acute allergic inflammation by indomethacin is reversed by prostaglandin E2: apparent correlation with in vivo modulation of mediator release.

The Pharmacology of Anaphylaxis in the Chicken Intestine

Effects of Modulators of Arachidonic Acid Metabolism on the Synthesis and Release of Slow‐reacting Substance of Anaphylaxis

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