Release of Mediators of Anaphylaxis: Inhibition of Prostaglandin Synthesis and the Modification of Release of Slow Reacting Substance of Anaphylaxis and Histamine

Abstract

1 When isolated perfused lungs from sensitized guinea-pigs were challenged with antigen, histamine, slow reacting substance of anaphylaxis (SRS-A) and prostaglandin-like substances were released into the effluent. 2 Treatment of the lungs before and during challenge with indomethacin (0.5-10 ig/ml), sodium aspirin (1-10 pg/ml), sodium meclofenamate (0.1-1 Mg/ml) or ketoprofen (0.5-5 /g/ml) inhibited the release of prostaglandins while increasing the output of histamine and SRS-A between threeand five-fold. 3 Diethylcarbamazine (0.2-1 mg/ml) reduced the release of SRS-A and histamine but increased the amount of prostaglandin-like substances produced. 4 Eicosatetraynoic acid (10 pg/ml) inhibited formation of prostaglandins but did not modify release of histamine and SRS-A. 5 The results with non-steroid anti-inflammatory drugs and diethylcarbamazine suggest that prostaglandins, or some other product of the cyclo-oxygenase system, depress the anaphylactic release of SRS-A and histamine.

Slow‐reacting substance of anaphylaxis Purification and characterisation

“…At all stages of purification, fractions were assayed for SRS-A activity on guinea-pig ileum [2]; slowreacting substance of anaphylaxis (SRS-A) was quantitated in arbitrary units defined in terms of the activity of an initial batch of partially purified material. 0.068 i: 0.004 units SRS-A are equivalent to 2 units SRS-A measured in terms of histamine [8].…”

“…After 21 days the animals were killed and their lungs perfused for 15 min with Tyrode solution containing 1 pg/ml of indomethacin. The lungs were then challenged with 10 mg ovalbumin (Sigma grade III) and the effluent collected on ice over a period of 10 min [2] . Activated charcoal was added to the crude effluent (0.25 g/l00 ml), which was then shaken and centrifuged at 2000 X g for 20 min.…”

“…Since then the roles of histamine and prostaglandins in asthma and anaphylaxis have been extensively studied. It has been found, by the development of chemical antagonists and later by the synthesis of pure mediators, that histamine accounts for only part of the bronchoconstriction of anaphylaxis or asthma, and that while some prostaglandins are bronchoconstrictors, their main action seems to be as modulators of the other agonists [2,3] .…”

The Effect of Inhibitors of Arachidonic Acid Metabolism on Drug‐induced Contractions in Isolated Tracheal Smooth Muscle of the Pig

“…However, an alternative explanation might be that indomethacin diverts arachidonic acid metabolism through the lipoxygenase pathway. This action of indomethacin has been shown to occur with the immunological release of SRS-A from perfused guinea-pig lungs (Engineer, Niederhauser, Piper & Sirois, 1978). If the lipoxygenase products thus formed were contractile then this could partly explain why indomethacin can enhance contractile responses in tracheal tissues.…”

ARACHIDONIC ACID METABOLISM AND MODULATION OF in vitro ANAPHYLAXIS BY 5,8,11,14‐EICOSATETRAYNOIC ACID AND 9a,12a‐OCTADECADIYNOIC ACID

“…It is well established that ETYA inhibits the antigeninduced release of SRS-A from actively sensitized chopped guinea-pig lung (Hitchcock, 1978;Piper, Tippins, Morris & Taylor, 1979;Watanabe-Sohno & Parker, 1980) and that indomethacin stimulates SRS-A release (Engineer, Niederhauser, Piper & Sirois, 1978;Hitchcock 1978;Watanabe-Sohno & Parker, 1980). Since Ro-3-1314 had similar effects to indomethacin on the antigen-induced contraction of guinea-pig trachea it was of interest to determine the effects of this fatty acid on SRS-A release from chopped guinea-pig lung.…”