Slow‐reacting substance of anaphylaxis Purification and characterisation

Morris, Howard R.; Taylor, Graham W.

doi:10.1016/0014-5793(78)80332-9

Cited by 104 publications

(19 citation statements)

References 11 publications

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“…Morris et al, 1978). This is clearly illustrated in Figure 4 which shows a reverse phase chromatogram of a sample of SRS-A which had been stored in the deep freeze in methanol for 7 days.…”

Section: Purification Proceduresmentioning

confidence: 93%

On the Preparation of Highly Purified Slow Reacting Substance of Anaphylaxis (Srs‐a) From Biological Extracts

Blackwell

Burka

Flower

et al. 1980

British J Pharmacology

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Very highly purified (> 100,000 u/mg) slow reacting substance of anaphylaxis (SRS‐A) has been prepared by reversed phase high pressure liquid chromatographic (HPLC) techniques. High resolution liquid chromatography suggests that SRS‐A may exist in at least three distinct forms which are possible tautomeric. SRS‐A collected by antigen challenge in vivo and by calcium ionophore‐induced release in vitro are chromatographically indistinguishable. Treatment of SRS‐A with diazomethane but not sodium borohydride results in a loss of biological activity but treatment of the methyl ester with base results in a partial recovery of activity. Highly purified SRS‐A was examined by infrared and ultra‐violet spectroscopy, and found to have a benzene‐aromatic and probably an amino acid.

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“…Morris et al, 1978). This is clearly illustrated in Figure 4 which shows a reverse phase chromatogram of a sample of SRS-A which had been stored in the deep freeze in methanol for 7 days.…”

Section: Purification Proceduresmentioning

confidence: 93%

On the Preparation of Highly Purified Slow Reacting Substance of Anaphylaxis (Srs‐a) From Biological Extracts

Blackwell

Burka

Flower

et al. 1980

British J Pharmacology

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“…Two biological activities derived from ionophore treatment of rat mononuclear cells in the presence of cysteine were separated by straight-phase HPLC (27) and two activities generated by anaphylactic challenge of guinea pig lung were resolved on RP-HPLC (15). Furthermore, multiple SRSs were generated from rat mononuclear cells with A23187 in the presence of different thiols (28).…”

Section: Chromatographymentioning

confidence: 99%

“…Recently, an ionophore-stimulated SRS from mouse mastocytoma cells designated as leukotriene C-1 (11) (LTC-1) was identified as 5(S)-hydroxy-6(R)-S-glutathionyl-7,9-trans,11,14-cts-icosatetraenoic acid (II in Fig. 1) (12, 13) and was prepared in quantity by total synthesis.This communication reports the use of synthetic leukotrienes C-1 (13) and D (IV) (LTD) to standardize retention times on high-performance liquid chromatography (HPLC) (14,15) and to calculate the specific functional activities of SRS-A produced by an anaphylactic reaction in the rat peritoneal cavity or human lung. Additionally, naturally derived SRS-A components were compared with the synthetic leukotrienes in regard to differential and specific activities on the guinea pig tracheal and lung parenchymal muscle strips in vitro (14, 16), UV absorption, and enzymic oxidation.…”

mentioning

confidence: 99%

Slow reacting substances of anaphylaxis: Identification of leukotrienes C-1 and D from human and rat sources

Lewis

Austen

Drazen

et al. 1980

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

365

102

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Slow reacting substance(s) of anaphylaxis (SRS-A) was isolated from both human (lung) and rat sources and compared with three synthetic SRS-As of known structureleukotrienes (LTs) C-1, C-2, and D. Reversed-phase liquid chromatography was used both as a final purification step and a means of comparison of biologically derived and synthetic substances. Two major peaks of SRS-A activity of both rat and human origin corresponded chromatographically with LTC-1 and LTD, respectively, and had equivalent specific activities on the guinea pig ileum. With guinea pig ileum, the specific activities (units/pmol) for synthetic leukotrienes and anaphylactic peaks were (mean -SEM): synthetic LTC-1, 1.93 -0.13; SRS-Arat peak I, 1.69 + 0.43; synthetic LTD, 6.10 i 1.15; SRS-Arat peak 11, 7.14 + 0.51; and SRS-AhU peak II, 1.90. Both synthetic LTC-1 and LTD and their SRS-A natural counterparts had a preferential contractile activity on guinea pig peripheral airway compared to central airways and were at least 200 times more active than histamine on peripheral airways on a molar basis. Leukotriene D is the major SRS-A of human lung and accounts for almost all of the biological activity. It likely is formed from leukotriene C-1 in vivo by an enzymic process of the well-known 'y-glutamyltransferase type.Although "slow reacting substance of anaphylaxis" (SRS-A) has been recognized as a putative major mediator of immediate hypersensitivity reactions for 40 years (1), only in the past decade have both proof of potency and evidence of chemical structure emerged. Brocklehurst (2) distinguished SRS-A from histamine in an anaphylactic perfusate by its contractile action on an (H-1) antihistamine-blocked guinea pig ileum wth a slow progression to maximal effect. Subsequent investigations established it to be a polar lipid (3, 4) with strong ultraviolet absorbance and possibly containing sulfur (4, 5). Cysteine was subsequently observed to augment generation of SRS-A (6) and a calcium ionophore was shown to stimulate production of nonanaphylactic slow-reacting substance (SRS) (7, 8) with incorporation of radiolabeled arachidonic acid as the lipid precursor (9, 10). Recently, an ionophore-stimulated SRS from mouse mastocytoma cells designated as leukotriene C-1 (11) (LTC-1) was identified as 5(S)-hydroxy-6(R)-S-glutathionyl-7,9-trans,11,14-cts-icosatetraenoic acid (II in Fig. 1) (12, 13) and was prepared in quantity by total synthesis.This communication reports the use of synthetic leukotrienes C-1 (13) and D (IV) (LTD) to standardize retention times on high-performance liquid chromatography (HPLC) (14,15) and to calculate the specific functional activities of SRS-A produced by an anaphylactic reaction in the rat peritoneal cavity or human lung. Additionally, naturally derived SRS-A components were compared with the synthetic leukotrienes in regard to differential and specific activities on the guinea pig tracheal and lung parenchymal muscle strips in vitro (14, 16), UV absorption, and enzymic oxidation. MATERIALS AND METHODSMaterials. ...

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“…Neither the material generated by immunologic reactions in the rat peritoneal cavity (1) or perfused guinea pig lung (3) nor that elicited by the action of divalent cation ionophore on preparations of rat peritoneal macrophages (4), leukemic basophils (5), or mast cells (6) has been structurally defined. We have previously demonstrated that intravenous infusion in the unanesthetized guinea pig of partially purified SRS-A results in a marked fall in dynamic pulmonary compliance but has little effect on pulmonary resistance (7).…”

Section: Introductionmentioning

confidence: 99%

Differential effects of a partially purified preparation of slow-reacting substance of anaphylaxis on guinea pig tracheal spirals and parenchymal strips.

Drazen¹,

Lewis²,

Wasserman³

et al. 1979

J. Clin. Invest.

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Slow‐reacting substance of anaphylaxis Purification and characterisation

Cited by 104 publications

References 11 publications

On the Preparation of Highly Purified Slow Reacting Substance of Anaphylaxis (Srs‐a) From Biological Extracts

On the Preparation of Highly Purified Slow Reacting Substance of Anaphylaxis (Srs‐a) From Biological Extracts

Slow reacting substances of anaphylaxis: Identification of leukotrienes C-1 and D from human and rat sources

Differential effects of a partially purified preparation of slow-reacting substance of anaphylaxis on guinea pig tracheal spirals and parenchymal strips.

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