Bradykinin, a Hypotensive and Smooth Muscle Stimulating Factor Released From Plasma Globulin by Snake Venoms and by Trypsin

Silva, M. Rocha e; Beraldo, W. T.; Rosenfeld, Greg

doi:10.1152/ajplegacy.1949.156.2.261

Cited by 779 publications

(180 citation statements)

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“…It was therefore decided to estimate instead the extractable histamine after precipitation of the proteins with TCA. Substance X, which shares some of the properties of bradykinin (Rocha e Silva, Beraldo, and Rosenfeld, 1949), may have appeared because of contact between plasma and glass (Armstrong, Jepson, Keele, and Stewart, 1954) or resin, or because the plasma was diluted with buffer (Schachter, 1956). Careful treatment of the blood and plasma by methods similar to those employed by Armstrong et al (1954) probably delayed the formation of substance X, so that when the plasma proteins were precipitated two to three hours after obtaining the blood samples, none was detectable in the solution for assay.…”

Section: Discussionmentioning

confidence: 99%

A Method of Estimating Histamine in Plasma

Adam

Hardwick

Spencer

1957

British Journal of Pharmacology and Chemotherapy

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The method is intended for the estimation of minute quantities of histamine in blood plasma. A neutralized trichloracetic acid extract of plasma is adsorbed at pH 8 on a column prepared by mixing a quantity of the cationic exchange resin Amberlite XE-64 with powdered cellulose as a supporting medium. Histamine is adsorbed but N-acetylhistamine is not: the amines can therefore be estimated independently. Elution of the histamine is by displacement with HCL. The eluate is converted into the solution for bioassay on the superfused guinea-pig ileum.In recovery experiments histamine was added in the range 25 to 100 ng. to solutions of known composition and to plasma (5 ml.) obtained from man and the cat. The mean recovery in this range for histamine added to plasma was 82.5% A2 S.E. (17 estimations).The histamine equivalent of human plasma obtained from the antecubital vein was found to be less than 1 ng./ml.It was possible by this method to follow the concentration of histamine in the arterial plasma of the cat when histamine was infused intravenously at a rate of 330 ng./kg./min. There was no perceptible change in the arterial blood pressure during the infusion, but the plasma histamine rose from <0.3 ng./ml. to 3.4 ng./ml. (mean of 2 estimations).When the quantity of histamine extractable from plasma is less than can be estimated by conventional methods of bioassay, the sensitivity of the test can be increased by applying the undiluted extract directly to the strip of guinea-pig ileum; this may be suspended in a minute bath (Mongar and Schild, 1950) or in air, as in the technique of superfusion (Gaddum, 1953). The method is applicable if the histamine has been sufficiently purified and if the test solution is similar in composition to the solution bathing the intestine between the doses.If plasma is extracted by the method of Barsoum and Gaddum (1935) as modified by Code (1937a) and tested in this way, the activity of the extract is only partially abolished by the histamine antagonist mepyramine maleate (Mongar and Whelan, 1953). Moreover, the method does not distinguish between free histamine and histamine which may be released from pharmacologically inactive forms at the stage of refluxing the extract in strong acid (unpublished results).Various chromatographic methods of purifying histamine have been proposed and are reviewed in the article by Code and McIntire (1956). Some employ paper chromatography, others weak cationic exchangers which are used to remove histamine from solutions containing organic solvents.These methods are designed mainly for the chemical determination of histamine, but some have been combined with bioassay.In the method to be described the purification is conducted entirely in aqueous solution with the aid of a carboxylic ion exchange resin, at room temperature and at pH values not far from neutral. Advantage is taken of the fact that carboxylic resins have a high exchange capacity and can be buffered over a wide range of pH. They can therefore be used to separate weak organic bases in a...

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Section: Discussionmentioning

confidence: 99%

A Method of Estimating Histamine in Plasma

Adam

Hardwick

Spencer

1957

British Journal of Pharmacology and Chemotherapy

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“…Histamine was assayed by measuring the contraction of an atropinized guinea pig ileum (16) . Chromatographically pure histamine was used as standards at concentrations of 5 and 10 ng/ml.…”

Section: Methodsmentioning

confidence: 99%

The selective eosinophil chemotactic activity of histamine.

Clark¹,

Gallin²,

Kaplan³

1975

The Journal of Experimental Medicine

246

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Histamine diphosphate was shown to selectively attract human eosinophils from mixed granulocyte populations when over 20% eosinophils were used in a modified Boyden chamber chemotactic assay system. This effect of histamine is abolished by incubation with diamine oxidase (histaminase) and was generated by decarboxylation of L-histidine. A linear dose dependent increase in eosinophil migration was observed between 3 X 10(-7) M and 1.25 X 10(-6) M, while higher concentrations of histamine inhibited the migration of eosinophils. The attractant activity of histamine was not inhibited by H-1 or H-2 receptor antagonists, however, the inhibition of migration observed at higher histamine concentrations was reversed by metiamine, an H-2 receptor antagonist. The effects of histamine upon eosinophil migration were demonstrable using three different assays: (a) counting cells that had traversed 5-mum pore, 12-mum thick polycarbonate filters, (b) counting cells that had migrated various distances into a 3-mum pore, 145-mum cellulose nitrate filters, or (c) measuring the number of cells that had traversed an upper polycarbonate filter and migrated into a lower cellulose nitrate filter using 15Cr-labeled cells. The ability of histamine to enhance eosinophil migration was shown to be dependent upon the presence of a concentration gradient; histamine did not cause a dose-dependent increase in random motility. Furthermore, preincubation of the eosinophils with histamine deactivate the cells to further stimulation by histamine or by C5a. It is concluded that in low doses histamine is a chemoattractant for human eosinophils, while in higher doses histamine inhibits eosinophil migration. These observations may relate to the influx and localization of eosinophils in immediate hypersensitivity reactions.

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“…Bradykinin was prepared by the action of crystalline trypsin on heated bovine serum globulin and was purified chromatographically (Lockhart and Jones, personal communication). The potencies of the various samples used, assayed on guinea-pig ileum against a standard preparation (Rocha e Silva, Beraldo and Rosenfeld, 1949), ranged from 7 to 900 units/mg. After the work described below was completed, Elliott, Lewis and Horton (1960) kindly provided us with a sample of pure bradykinin; and comparison with our reference preparation indicated that about 12,000 to 12,500 units were equivalent to 1 mg. pure bradykinin, or that 1 unit was equivalent to about 80 ng.…”

Section: Methodsmentioning

confidence: 99%

The Bronchoconstrictor Action of Bradykinin in the Guinea‐pig

Collier

Holgate

Schächter

et al. 1960

British Journal of Pharmacology and Chemotherapy

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Bradykinin was found to be a potent bronchoconstrictor agent in the guinea-pig anaesthetized with urethane. This action was not affected by vagotomy, or by treatment of the animal with mepyramine, atropine, lysergic acid diethylamide, or cortisone. Adrenaline and isoprenaline suppressed the bronchoconstrictor responses to bradykinin and histamine. Small doses of acetylsalicylic acid, however, suppressed only that to bradykinin. Bradykinin also produced bronchoconstriction in the isolated perfused lungs of the guinea-pig. The closely related peptide, wasp kinin, was also a potent bronchoconstrictor.

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Bradykinin, a Hypotensive and Smooth Muscle Stimulating Factor Released From Plasma Globulin by Snake Venoms and by Trypsin

Cited by 779 publications

References 0 publications

A Method of Estimating Histamine in Plasma

A Method of Estimating Histamine in Plasma

The selective eosinophil chemotactic activity of histamine.

The Bronchoconstrictor Action of Bradykinin in the Guinea‐pig

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