Release of Slow-Reacting Substance of Anaphylaxis in the Rat: Polymorphonuclear Leukocyte

Orange, Robert P.; Valentine, Martin D.; Austen, K. Frank

doi:10.1126/science.157.3786.318

Cited by 29 publications

(11 citation statements)

References 14 publications

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“…Microembolization has been associated with histamine release (14), and circulating platelets were decreased rapidly in the course of a perfusion. If platelets or other formed elements help mediate histamine release, they may do so either directly or possibly via effects associated with plasma reactions, such as complement activation or formation of slow-reacting substance (15).…”

Section: Discussionmentioning

confidence: 99%

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Role of Histamine in Hypoxic Pulmonary Hypertension in the Rat

Hauge

Melmon

1968

Circulation Research

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The present investigation was undertaken to see if any of the naturally occurring vasoactive substances was likely to act as a mediator for the pulmonary vasoconstrictor response to acute alveolar hypoxia. Rats were treated with agents that deplete local stores of vasoactive amines or inhibit their synthesis. Lungs from these animals were isolated, ventilated, and perfused with homologous blood at constant volume inflow. Their pressor responses to 2-to 3-minute periods of ventilation hypoxia (2% O 2 ) were observed.The histamine-releasing agent 48/80 or the histidine decarboxylase inhibitor NSD 1055, or both, depleted 73% of the histamine in the lung but had no consistent effect on the pressor responses to hypoxia. When 48/80 (0.2 to 1 mg) was given in vitro, histamine in the lung was reduced to 10% of normal, or less, and the pressor response to alveolar hypoxia was completely abolished.Reserpine, guanethidine, or alpha-methyl-tyrosine reduced catecholamine stores in heart tissue (as an index of general tissue changes) by a maximum of 90% and reserpine decreased serotonin in the lung by 93% without inhibiting the hypoxic pressor responses. The findings strengthen the concept that histamine mediates the pressor response to acute alveolar hypoxia in the rat.ADDITIONAL KEY WORDS reserpine guanethidine alpha-methyl-tyrosine blood platelets 48/80 NSD 1055 rat lungs• Histamine long has been known as a potent constrictor of pulmonary vessels (1). An investigation of the role of vasoactive substances as mediators of the pulmonary vasoconstrictor response to acute hypoxia suggested that endogenous histamine was important for this response (2). The approach was mainly to use a series of pharmacologic agents that blocked the action of a variety of naturally occurring pressor substances. In the present work we have tried to approach this problem by another route. The vasoactive amines in the lung were reduced by agents that depleted their stores and inhibited their synthesis, and the effect of these procedures on the pressor response to alveolar hypoxia was observed. The importance of blood platelets and serotonin in platelets was also evaluated. The results support the concept that endogenous histamine plays an important role in the hypoxic pulmonary pressor response in the rat. Materials and MethodsPreparation.-Isolated rat lungs were perfused with heparinized homologous blood at 37 to 38 °C under conditions of constant-volume, pulsatile inflow, and ventilated with a positive-pressure pump. The pulmonary arterial pressure (PPA), the ventilation overflow volume and the oxygen tension in the effluent blood were recorded continuously. The left atrial pressure was kept at 2 to 4 cm of water in each experiment.

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Section: Discussionmentioning

confidence: 99%

“…Such reduction had no apparent effect on the pressor responses to alveolar hypoxia nor on the pressor responses to injections of ATP (250 fxg) or bradykinin (15 …”

mentioning

confidence: 98%

Role of Histamine in Hypoxic Pulmonary Hypertension in the Rat

Hauge

Melmon

1968

Circulation Research

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“…Since the polymorphonuclear leukocyte is required for optimal SRS-Arat release ( 15), the effect of Hetrazan on the number and type of circulating white cells was determined.…”

Section: Eflect Of Hetrazan On the Antigen-induced Release Of Srs-a Rmentioning

confidence: 99%

“…The administration of cobra venom (Naja haje) is also known to suppress the release of SRS-Arat (15). Whether this action is through a direct effect on the complement system or through some unrelated activity is not known.…”

Section: Eflect Of Hetrazan On the Antigen-induced Release Of Srs-a Rmentioning

confidence: 99%

Inhibition of the Release of Slow-Reacting Substance of Anaphylaxis in the Rat with Diethylcarbamazine

Orange

Valentine

Austen

1968

Experimental Biology and Medicine

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“…It has been shown that rabbit and rat an tiserum can each sensitise the peritoneal cavity of the rat for the release, by antigen, of slow-reacting substance of anaphylaxis (SRS-A) without the release of histamine [13,20] and the source of the SRS-A was not the mast cell but possibly the neutro philic polymorphonuclear leucocytes [19]. The sensitising antibody, in the rat antise rum, was an immunoglobulin Ga [13] (more recently classified as IgG2a [2]).…”

Section: Introductionmentioning

confidence: 99%

Rat Passive Peritoneal Anaphylaxis Following Sensitisation with Guinea Pig Antiserum: an Immediate Hypersensitivity Reaction without Histamine Release

Smith¹,

Ross²,

Spicer³

1980

Int Arch Allergy Immunol

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Antigen challenge of rats, sensitised by an intraperitoneal injection of guinea pig antiserum, produced an antibody-dependent increase in concentrations, in the peritoneal fluids, of slow-reacting substance of anaphylaxis (SRS-A) and of extravasated, dye-labelled, plasma proteins but not of histamine or 5-hydroxytryptamine. The SRS-A released may not be the main mediator of the extravasation since pre-treatment of the rats with the SRS-A antagonists FPL 55712 and BRL 19880 had no effect on extravasation, and a number of compounds, given in a similar way, were more potent as inhibitors of SRS-A release than of extravasation. Rat passive peritoneal anaphylaxis (PPA), following sensitisation with guinea pig antiserum, provides an example of an immediate hypersensitivity reaction in which there is no antibody-dependent release of histamine and in which the SRS-A released may not mediate all of the extravasation produced.

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Release of Slow-Reacting Substance of Anaphylaxis in the Rat: Polymorphonuclear Leukocyte

Cited by 29 publications

References 14 publications

Role of Histamine in Hypoxic Pulmonary Hypertension in the Rat

Role of Histamine in Hypoxic Pulmonary Hypertension in the Rat

Inhibition of the Release of Slow-Reacting Substance of Anaphylaxis in the Rat with Diethylcarbamazine

Rat Passive Peritoneal Anaphylaxis Following Sensitisation with Guinea Pig Antiserum: an Immediate Hypersensitivity Reaction without Histamine Release

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