A Family of Long-Acting Depressors

Baltzly, Richard; Buck, Johannes S.; Beer, Edwin J. de.; Webb, F. J.

doi:10.1021/ja01172a045

Cited by 140 publications

(34 citation statements)

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“…Here we present our studies on the purification and identification of two SRSs from cat paws after perfusion with Compound 48/80 (16) and biochemical evidence supporting the contention that SRS I corresponds to SRS-A. (,uC18) preparative column (0.94 X 50 cm) of Partisil-10 M9 ODS (Whatman) was used for SRS purification.…”

supporting

confidence: 53%

Identification of the slow reacting substances from cat paws.

Houglum¹,

Pai²,

Atrache³

et al. 1980

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

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Perfusion of cat paws with compound 48/80 released two slow reacting substances (SRSs) which were isolated and characterized as 5-hydroxy-S-cysteinylglycyl-7,9,-11,14-icosatetraenoic acid (SRS I) and -hydroxy-6S-cysteinyl-7,9,11,14-icosatetraenoic acid (SRS II) on the basis of chemical degradations, amino acid analyses, spectroscopic and enzymic experiments, and comparison with synthetic samples. The smooth muscle-contractile activities of synthetic 5-hydroxy-6 y-glutamylcysteinylglycyl-7,9,11,14-icosatetraenoic acid, synthetic5-hydroxy--S-cysteinyl-7,9,11,14-icosatetraenoic acid, and SRS II were not inactivated by arylsulfatase. On the other hand, the spasmogenic activities produced by synthetic 5-hydroxy-6S-cysteinylglycyl-7,9,11,14-icosatetraenoic acid and SRS I were destroyed at the same rate by the arylsulfatase. This mode of inactivation was attributed to an aminopeptidase activity in the arylsulfatase preparation because 5-ydroxyl-6-Scysteinyl-7,9,11,14-icosatetraenoic acid was isolated and identified as the reaction end product. Because the properties of SRS from cat paws closely resemble those of SRS generated by immunological stimulation of human tissues (SRS-A) and because all known SRS-A are inactivated by arylsulfatases, we contend that 5-hydroxy-6S-cysteinylglycyl-7,9,11,14-icosatetraenoic acid (SRS I) corresponds to SRS-A.In 1938, Feldberg and Kellaway (1) first described a substance that caused the guinea pig ileum to contract more slowly and with more sustained action than did histamine; they named the compound "slow reacting substance (SRS)." Two years later, Kellaway and Trethewie (2) reported that slow reacting substance of anaphylaxis (SRS-A) was released from sensitized tissue by a specific antigen. Subsequently, it was shown (3) that SRS-A was one of several pharmacologic mediators that may be important in human asthma. SRS has since been found to be released from many types of tissues and cell suspensions including guinea pig, rabbit, monkey, bovine, and human lungs (4-6), cat paws (7,8), isolated rat mast cells (9), human leukocytes (10) and nasal polyps (11), human and rat leukemic basophils (12,13), and rat peritoneal fluid (14, 15).Here we present our studies on the purification and identification of two SRSs from cat paws after perfusion with Compound 48/80 (16) (,uC18) preparative column (0.94 X 50 cm) of Partisil-10 M9 ODS (Whatman) was used for SRS purification. The radial compression separation system consisted of a Waters radial compression module (RCM-100) with a radial-Pak C18 cartridge (0.8 X 10 cm).SRS Assay. SRS bioactivity was assayed on guinea pig ileum segments by a modification of the procedure reported by Chakravarty (17). Histamine was assayed in the presence of atropine (1 MM) and SRS was assayed in the presence of atropine (1 ,uM) and mepyramine (1 ,M). One unit of SRS was defined as that amount of SRS which caused a contraction with a peak height equal to that induced by 5 ng of histamine base. After the log-dose-response curve for histamine was determin...

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supporting

confidence: 53%

Identification of the slow reacting substances from cat paws.

Houglum¹,

Pai²,

Atrache³

et al. 1980

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

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“…The present investigation is part of an attempt to prove an old hypothesis, namely, that this increase in permeability is mediated by histamine. A comparative study was made of histamine, of the histamineliberator 48/80, a condensation product ofp-methoxyphenylethylmethylamine and formaldehyde (Baltzly, Buck, de Beer & Webb, 1949), and of leukotaxine (Menkin, 1936(Menkin, , 1938a.In animals with a recently injected vital dye in their blood, the intradermal injection of substances that increase permeability of the blood vessels is followed by an accumulation of dye at the site of injection, presumably due to the passage of an excess of dye-stained plasma into the tissue spaces. When the blood flow and the vascular bed of the skin are relatively constant, differences in the size and intensity of stained areas of skin reflect differences in vascular permeability, and may be used to investigate the properties of substances that increase permeability in this way.…”

mentioning

confidence: 99%

Vascular reactions to histamine, histamine‐liberator and leukotaxine in the skin of guinea‐pigs

Miles¹,

Miles²

1952

The Journal of Physiology

489

267

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A substantial increase in capillary permeability is a feature of acute inflammation in bacterial infections. The present investigation is part of an attempt to prove an old hypothesis, namely, that this increase in permeability is mediated by histamine. A comparative study was made of histamine, of the histamineliberator 48/80, a condensation product ofp-methoxyphenylethylmethylamine and formaldehyde (Baltzly, Buck, de Beer & Webb, 1949), and of leukotaxine (Menkin, 1936(Menkin, , 1938a.In animals with a recently injected vital dye in their blood, the intradermal injection of substances that increase permeability of the blood vessels is followed by an accumulation of dye at the site of injection, presumably due to the passage of an excess of dye-stained plasma into the tissue spaces. When the blood flow and the vascular bed of the skin are relatively constant, differences in the size and intensity of stained areas of skin reflect differences in vascular permeability, and may be used to investigate the properties of substances that increase permeability in this way. Our work was confined to the skin of guinea-pigs, partly because much is already known about skin reactions to toxins and other inflammatory agents, and partly because it is a tissue readily studied in the intact and unanaesthetized animal-an important consideration with phenomena which, like the passage of dye through vascular endothelium, are peculiarly dependent on the state of the blood vessels in the tissue under test. MATERIALS AND METHODSAlbino guinea-pigs, 300-450 g in weight, were used throughout. The skin of the trunk was depilated, after clipping away the hair, by a paste consisting of wheat flour, 350 g; talcum powder, 350 g; barium sulphide, 250 g; Castile soap powder, 50 g; and water. The depilated area was thoroughly washed with warm water.Detection of increawed permeability. Neither the intradermal injection nor the pricking-in of histamine or 48/80 produce in the depilated skin any measurable reaction indicating change in

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“…Compound 48/80 as reported by Baltzly, Buck, de Beer, and Webb (1949) is a polymer of Nmethylhomoanisylamine and formaldehyde. Although similar LD 50's have been obtained with different batches of Compound 48/80 (Dews, Wnuck, Fanelli, Light, Tornaben, Norton, Ellis, and de Beer, 1953), it was felt desirable to have an assay method which might be more closely related to the histamine-liberating property of 48/80.…”

mentioning

confidence: 76%

“…

Compound 48/80 as reported by Baltzly, Buck, de Beer, and Webb (1949) All solutions were at room temperature. Usually two pieces of mesentery were used in each concentration of drug.

…”

mentioning

confidence: 99%

Quantitative Determination of Mast Cell Fragmentation by Compound 48/80

Norton¹

1954

British Journal of Pharmacology and Chemotherapy

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Compound 48/80 as reported by Baltzly, Buck, de Beer, and Webb (1949) All solutions were at room temperature. Usually two pieces of mesentery were used in each concentration of drug. From these pieces five microscope fields were selected at random under 100 x magnification from widely separated areas of the mesentery. In each field, using 430 x magnification, the first 10 mast cells were examined, starting from the lefthand side of the field and proceeding clockwise. For each drug concentration 50 cells were counted and the percentage of disrupted cells was obtained. Each cell was considered either "disrupted" or ".not disrupted." The term " disrupted " was selected instead of " fragmented," since granules were found around many cells which did not appear to be in fragments. Fawcett (1954) has also reported this phenomenon. The sole criterion for calling a cell " disrupted " was the presence of granules outside the cell. Many cells which did not show extrusion of granules appeared swollen at low concentrations of 48/80.For evaluating the percentage disruption the labels of the slides were covered and the slides were counted in random sequence. RESULTS Comparison

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A Family of Long-Acting Depressors

Cited by 140 publications

References 0 publications

Identification of the slow reacting substances from cat paws.

Identification of the slow reacting substances from cat paws.

Vascular reactions to histamine, histamine‐liberator and leukotaxine in the skin of guinea‐pigs

Quantitative Determination of Mast Cell Fragmentation by Compound 48/80

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