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

Drazen, Jeffrey M.; Lewis, Robert A.; Wasserman, Stephen I.; Orange, Robert P.; Austen, K. Frank

doi:10.1172/jci109262

Cited by 75 publications

(27 citation statements)

References 24 publications

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“…SRS-A is generated by IgE-dependent pathways in human lung fragments and dispersed lung cells (17), and human small airway muscle is exquisitely reactive to SRS-Ahu (3). The prominence of peripheral airway constriction in bronchial asthma (21) may relate to the selective action of SRS-A on the peripheral airways, as shown in vvo in both the guinea pig (22) and the rhesus monkey (23) and in vitro in guinea pig tissues (14).…”

Section: Chromatographymentioning

confidence: 99%

“…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%

“…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%

“…SRS-A was produced by IgGa-dependent pathways in the rat peritoneal cavity (4) and by IgE-dependent activation of human lung fragments (17) and was isolated by elution from XAD-8, DE-52 cellulose, and silicic acid columns as described (14).…”

mentioning

confidence: 99%

“…Standardization was achieved by defining 1 unit of activity as that produced by a 5 ng/ml solution of histamine as described (2). The contractile effects of LTC-1, LTD, SRS-Arat, and SRS-AhU were additionally evaluated with guinea pig tracheal spirals and parenchymal strips (14,16). Concentration-effect relationships for the constriction of each tissue by histamine were determined by exposing the tissue to histamine, subjecting it to overflow wash with Tyrode's solution, and allowing it to return to its baseline tension, usually in about 40-60 min.…”

mentioning

confidence: 99%

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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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Section: Chromatographymentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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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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Lung Metabolism of Eicosanoids: Prostaglandins, Prostacyclin, Thromboxane, and Leukotrienes

Bakhle

Ferreira

1985

Comprehensive Physiology

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History of Eicosanoids Overview of Eicosanoid Biosynthesis Antagonists of Eicosanoids and Inhibitors of Their Synthesis Lung Pharmacology of Eicosanoids Inactivation of Eicosanoids in Lung Synthesis of Eicosanoids by LungSynthesis from exogenous arachidonic acid Synthesis from endogenous arachidonic acid Release of eicosanoids after anaphylactic reactions Release of eicosanoids by mechanical stimulation Release of eicosanoids by endogenous mediators Summary SINCE THE RENAISSANCE of interest in metabolic functions of the lung in the late 1960s, our knowledge of these functions has grown at an exponential rate common to many fields of research. Within this rapidly growing field, however, one area has expanded in an almost explosive manner: the study of the metabolism of arachidonic acid (AA) and its oxygenated metabolites in the lung. These metabolites [prostaglandins (PGs), prostacyclin, thromboxanes, and leukotrienes] are all, like AA, basically molecules containing 20 carbon atoms. Because the chemical name for AA is eicosatrienoic acid, these metabolites and their precursors are often called eicosanoids.An early paper on PG biosynthesis demonstrated a highly active enzyme in guinea pig lung extracts (16), and the most recent advance in eicosanoid biochemistry was the identification of leukotrienes generated by lung tissue during anaphylaxis (195). These developments increased our knowledge of the lung and are important and sometimes essential elements in the development of our understanding of the eicosanoids in general. HISTORY OF EICOSANOIDS

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Chemical Mediators of Immediate Hypersensitivity Reactions

Drazen

1986

Comprehensive Physiology

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

Cited by 75 publications

References 24 publications

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

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

Lung Metabolism of Eicosanoids: Prostaglandins, Prostacyclin, Thromboxane, and Leukotrienes

Chemical Mediators of Immediate Hypersensitivity Reactions

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