thromboxane-a2 and Anaphylaxis

Topics: Anaphylaxis; Animals; Asthma; Bronchi; Dinoprost; Dinoprostone; Dogs; Epoprostenol; Guinea Pigs; Humans; In Vitro Techniques; Lung; Lung Diseases; Models, Biological; Muscle, Smooth; Prostaglandin D2; Prostaglandins; Prostaglandins D; Prostaglandins E; Prostaglandins F; SRS-A; Thromboxane A2

Topics: Anaphylaxis; Animals; Arachidonic Acids; Cyclooxygenase Inhibitors; Digestive System; Epoprostenol; Fatty Acids; Humans; Inflammation; Prostaglandin Endoperoxides; Prostaglandins; Thromboxane A2; Thromboxane-A Synthase; Thromboxanes

1-[3-(4-Benzhydryl-1-piperazinyl)propyl]-3-(1H-imidazol-1-ylmethyl )- 1H-indole-6-carboxylic acid (CAS 172544-75-1, KY-234) was characterized pharmacologically. KY-234 (10(-9)-10(-6) mol/l) and ozagrel (10(-8)-10(-5) mol/l) inhibited the production of thromboxane A2 (TXA2) in rabbit platelets. KY-234 and pyrilamine at concentrations of 10(-9)-10(-6) mol/l relaxed the isolated guinea pig trachea contracted with histamine, while neither drug attenuated the heart rate increased by histamine. Cimetidine antagonized histamine in the right atrium but not in the trachea. KY-234 (10(-8)-10(-5) mol/l) and ozagrel (10(-7)-10(-4) mol/l), but not pyrilamine, attenuated the contraction induced by leukotriene D4 (LTD4) and platelet-activating factor in the lung parenchymal strips. In anesthetized guinea pigs, KY-234 (1-10 mg/kg p.o.) inhibited the LTD4- and histamine-induced bronchoconstriction. Ozagrel and terfenadine inhibited only the LTD4- and histamine-induced constrictions. KY-234 (3-30 mg/kg p.o.) inhibited the anaphylactic bronchoconstriction continuously for 15 min after antigen-challenge. Terfenadine (3-30 mg/kg p.o.) inhibited the constriction more strongly within the first 5 min (fast phase) than it did within 5 to 15 min (slow phase) after the challenge. Ozagrel (100 mg/kg p.o.) slightly attenuated only the constriction during the slow phase. These findings demonstrated that KY-234 has a selective TXA2 synthetase-inhibitory and H1-blocking activity and protects against anaphylactic bronchospasm more effectively than a TXA2 synthetase inhibitor or H1-blocker alone.

Topics: Anaphylaxis; Animals; Bronchial Spasm; Bronchoconstriction; Enzyme Inhibitors; Guinea Pigs; Histamine H1 Antagonists; In Vitro Techniques; Indoles; Leukotriene D4; Lung; Male; Methacrylates; Platelet Activating Factor; Rabbits; Thromboxane A2; Thromboxane-A Synthase; Trachea

The effects were studied of three novel thromboxane A2 (TXA2) receptor antagonists (S-1452, AA-2414 and ONO-3708) on the increase in pulmonary pressure caused by Forssman anaphylaxis in guinea-pigs. Three TXA2 antagonists at doses of between 1 and 10 mg/kg administered orally 1 h before the challenge clearly inhibited the pulmonary pressure increase. At a dose of 10 mg/kg, all three antagonists inhibited the pulmonary pressure increase caused by leukotriene D4 (LTD4) and U-46619, but not that caused by histamine. The decrease in peripheral platelet counts caused by Forssman anaphylaxis was also clearly inhibited by the three TXA2 antagonists. However, the decreased peripheral leukocyte counts were unaffected by the three agents. The decrease in serum complement activity (CH50) was inhibited by S-1452 and AA-2414 at a dose of 10 mg/kg. In bronchoalveolar lavage fluid (BALF), significant increases in eosinophils and neutrophils were observed after Forssman anaphylaxis. Three TXA2 antagonists at a dose of 10 mg/kg (except for AA-2414 on eosinophils) did not affect the changes of leukocyte counts in BALF. Moreover, increases in the TXB2 and 6-keto-PGF1 alpha levels of the BALF brought about by Forssman anaphylaxis were unaffected by the three TXA2 receptor antagonists. Histamine and LTD4 were not changed in the BALF after Forssman anaphylaxis. These results indicate the efficacy of TXA2 receptor antagonists on the increase in pulmonary pressure caused by Forssman anaphylaxis in guinea-pigs by direct antagonism to released TXA2.

Topics: 6-Ketoprostaglandin F1 alpha; Airway Resistance; Anaphylaxis; Animals; Antibodies, Heterophile; Benzoquinones; Bridged Bicyclo Compounds; Bronchoalveolar Lavage Fluid; Fatty Acids, Monounsaturated; Guinea Pigs; Heptanoic Acids; Histamine; Leukocyte Count; Male; Platelet Count; Quinones; Receptors, Prostaglandin; Receptors, Thromboxane; SRS-A; Thromboxane A2; Thromboxane B2

This study was designed to examine whether an inhaled beta 2-agonist, procaterol, inhibits thromboxane A2 (TXA2) production induced by antigen challenge in passively sensitized guinea-pigs in vivo. Antigen-induced bronchoconstriction was markedly inhibited by pre-treatment with procaterol. Inhaled procaterol significantly reduced in a dose-dependent manner the increment in TXB2 concentration in bronchoalveolar lavage fluid obtained 5 min after antigen challenge. Aerosol administration of procaterol significantly inhibited bronchoconstriction induced by inhaled histamine. These results suggest that inhalation of procaterol has an inhibitory effect on antigen-induced TXA2 production as well as a protective effect against bronchoconstriction induced by bronchoactive agents.

Topics: Administration, Inhalation; Anaphylaxis; Animals; Antigens; Bronchi; Bronchoalveolar Lavage Fluid; Bronchodilator Agents; Ethanolamines; Guinea Pigs; Histamine; Male; Methacrylates; Procaterol; Prostaglandins; Thromboxane A2; Thromboxane-A Synthase

Nimesulide (4-nitro-2-phenoxymethane sulfonanilide, Aulin, Mesulid) is a non-steroidal anti-inflammatory compound which shows antihistaminic activity and inhibits the immune release of histamine. The antihistaminic activity of this compound is specific for H1-receptor and has been demonstrated on isolated strips of guinea-pig trachea and on histamine-induced multiphasic inotropic response in left atria of guinea pig electrically driven. The effect of nimesulide is of non competitive type and, at the concentration of 1 x 10(-5) mol/l, is nearly 2 time less potent than pyrilamine (mepyramine) at 1 x 10(-6) mol/l. Nimesulide (1.6 mumol/kg i.v.) inhibits both bronchoconstriction (69%) and TXB2 formation (93%) induced by histamine (0.05 mumol/kg i.v.) in anaesthetized guinea-pigs. In contrast indomethacin (1.6 mumol/kg i.v.) decreases the generation of TXB2 (89%) without affecting the enhancement in tracheal insufflation pressure induced by histamine. In actively sensitized guinea-pigs both nimesulide and indomethacin protect the animals from deadly anaphylactic crisis. The rise in tracheal pressure induced by the antigenic challenge is inhibited of 80% and 63% respectively by nimesulide and indomethacin (6.4 mumol/kg i.v.). At this dose the two compounds reduced of 90% approximately the immunological release of TXB2 in the circulation. The release of histamine, induced by the anaphylactic reaction caused in perfused lungs obtained from actively sensitized guinea-pigs, is lessened by nimesulide (EC50 = 3.06; fid. lim. 2.59-3.63 mumol/l) and potentiated by indomethacin (EC50 = 0.89; fid. lim. 0.67-1.17 mumol/l).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Airway Resistance; Anaphylaxis; Animals; Anti-Inflammatory Agents, Non-Steroidal; Aorta, Thoracic; Blood Pressure; Guinea Pigs; Histamine; Histamine H1 Antagonists; In Vitro Techniques; Indomethacin; Lung; Male; Muscle Contraction; Muscle, Smooth; Muscle, Smooth, Vascular; Myocardial Contraction; Rabbits; Sulfonamides; Thromboxane A2; Trachea

In an IgE and an IgG model of anaphylaxis in the guinea pig, we investigated the role of prostanoids and PAF-acether in the tracheal response in vitro to immunochallenge. Indomethacin (10(-6) M) potentiated the antigen-induced contraction in both models suggesting the synthesis of relaxant prostaglandins during the anaphylactic phenomenon. UK-38,485 (10(-5) M), a thromboxane (TxA2) synthetase inhibitor, did not modify the tracheal response in the IgE model. In the IgG model, this drug reduced the response of the tracheal strips to antigen. Ro 19-3704 (10(-6) M) and BN 52021 (10(-5) M), two potent PAF antagonists, reduced antigen-induced contraction of the tracheal strips in the IgE model. These two drugs did not modify the contractile response in the IgG model. These results indicate that PAF-acether and TxA2 play a role in the IgE and IgG model of anaphylaxis, respectively.

Topics: Anaphylaxis; Animals; Antigens; Glyceryl Ethers; Guinea Pigs; Immunoglobulin E; Immunoglobulin G; In Vitro Techniques; Indomethacin; Muscle Contraction; Platelet Activating Factor; Thiazoles; Thromboxane A2; Trachea

Topics: Anaphylaxis; Animals; Azepines; Cyclooxygenase Inhibitors; Guinea Pigs; Heart; In Vitro Techniques; Indomethacin; Leukotrienes; Lipoxygenase Inhibitors; Naphthoquinones; ortho-Aminobenzoates; Platelet Activating Factor; Thromboxane A2; Triazines; Triazoles

LG 30435 is a new quarternary phenothiazine derivative with H1-antihistaminic and antimuscarinic properties. The ability of LG 30435 to prevent changes in respiratory mechanics, induced by different mediators and the immunological reaction, was monitored together with biological and radioimmunological determination of circulating thromboxane-A2 (TxA2) in anaesthetized guinea-pigs. LG 30435 dose-dependently reduces the bronchoconstriction and TxA2 generation caused by different stimuli such as histamine, acetylcholine, leukotriene C4 (LTC4) and PAF-acether. In addition i.v. and aerosol administration of LG 30435 causes a dose-dependent reduction of the increase in airway resistance and TxA2 generation induced by ovalbumin challenge in actively sensitized animals. LG 30435 infused at different concentrations through the isolated guinea-pig lungs inhibits the TxB2 generation caused by different anaphylactic mediators, but not by arachidonic acid. These data, which further substantiate the bronchodilator activity of LG 30435 against a variety of stimuli and demonstrate its protective properties on lung anaphylaxis, suggest that this compound has a potential therapeutic value in the treatment of asthma.

Topics: Anaphylaxis; Animals; Asthma; Bronchial Spasm; Bronchodilator Agents; Dose-Response Relationship, Drug; Guinea Pigs; Male; Phenothiazines; Respiratory Mechanics; Thromboxane A2

An anaphylactic reaction was induced with the specific antigen (1 mg Ovalbumin) in perfused lungs from actively sensitized guinea-pigs in order to evaluate the ability of the ginkgolide BN-52021 (0.4, 4, 40 micrograms/ml) to modulate the mediator release. The ginkgolide reduces in a dose dependent manner the release of histamine (22%, 45% and 75% of inhibition), TXB2 (77% of inhibition at the maximal dose used) and of SRS-A to a lower extent (only 33% at the higher dose). BN-52021 was still powerful in reducing histamine release induced by immunological reaction in indomethacin treated animals. In conclusion, the present "in-vitro" results confirm the beneficial activity of this ginkgolide, already demonstrated by the same Authors in "in-vivo" experiment, in anaphylactic reactions, and further substantiate the wider spectrum of action of the ginkgolide beside its specific PAF receptor antagonistic activity.

Topics: Anaphylaxis; Animals; Diterpenes; Ginkgolides; Guinea Pigs; Histamine; Histamine Release; Kinetics; Lactones; Lung; Male; Ovalbumin; SRS-A; Thromboxane A2; Thromboxane B2; Thromboxanes

Resistance to lung inflation and blood pressure were monitored together with biological and radioimmunological determination of circulating thromboxane A2 (TxA2) in anaesthetized guinea-pig. Bamifylline, a 2-benzyl-[4,5-d]-imidazopyrimidine derivative, and theophylline were compared for their antagonistic activity against the pulmonary effect of histamine (0.05 mumol/kg i.v.), leukotriene C4 (LTC4, 0.016 mumol/kg i.v.), platelet-activating factor (PAF, 0.0002 mumol/kg i.v.) and acetylcholine (0.1 mumol/kg i.v.). Bamifylline, as well as theophylline, showed a dose-dependent antagonistic activity against both bronchoconstriction and TxA2 generation induced by the above agonists. However, except for histamine where the two compounds were equiactive, bamifylline was 2 times more potent than theophylline. The maximal inhibitory activity was found against bronchoconstriction induced by PAF (ED50 = 6.5 mumol/kg i.v.) followed by histamine (ED50 = 9.5 mumol/kg i.v.), acetylcholine (ED50 = 24.3 mumol/kg i.v.) and LTC4 (ED50 = 31.6 mumol/kg i.v.). Bamifylline (3, 10, 30, 100 mumol/kg i.v.) and theophylline (3, 10, 30, 100 mumol/kg i.v.) protected guinea-pig from antigen-induced bronchoconstriction and TxA2 generation in ovalbumin actively sensitized animals. Also in this series of experiments bamifylline was more potent than theophylline, the ED50 being 9.3 mumol/kg i.v. and 22.9 mumol/kg i.v., respectively. These pharmacological data represent new support for the protecting effect of bamifylline against respiratory damage induced by well known anaphylaxis mediators.

Topics: Acetylcholine; Airway Resistance; Anaphylaxis; Animals; Bronchodilator Agents; Guinea Pigs; Histamine; Male; Platelet Activating Factor; SRS-A; Theophylline; Thromboxane A2

Topics: Acetylcholine; Anaphylaxis; Animals; Guinea Pigs; Histamine; In Vitro Techniques; Lung; Male; Muscle Contraction; Muscle, Smooth; SRS-A; Thromboxane A2; Trachea

To study the role of thromboxane (Tx) A2 in Forssman systemic shock (FSS) in guinea pig, the effect of (E)-3-[p-(1H-Imidazol-1-ylmethyl)phenyl]-2-propenoic acid hydrochloride (OKY-046), a specific Tx A2 synthetase inhibitor, was studied. OKY-046 administered intravenously clearly prolonged survival time and protected against fatal shock. In shocked animals, definite decreases in serum complement hemolytic activity (CH50), leucocyte counts and platelet counts and an increase in lactate dehydrogenase (LDH) activity were observed. In addition, a significant increase of Tx B2 and incoagulability of blood were observed after shock. Whereas OKY-046 had no effect on the decreases in CH50, platelet counts and leucocyte counts, it inhibited the increase of Tx B2 and increased the amount of 6-keto PG F1 alpha. When Forssman antibody (half a lethal dose) was injected, a diphasic increase in airway resistance was observed. OKY-046 inhibited this diphasic increase in airway resistance. These data suggest a pathophysiological role for Tx A2 in FSS. OKY-046 inhibited the Forssman antibody induced respiratory disorders probably due to the inhibition of Tx A2 synthesis after shock.

Topics: Acrylates; Airway Resistance; Anaphylaxis; Animals; Benzamidines; Female; Forssman Antigen; Guanidines; Guinea Pigs; Male; Methacrylates; Thromboxane A2; Thromboxane-A Synthase

In this paper we report an inhibitory effect of (-)-baclofen on many models of bronchial hyperreactivity both in vivo and in vitro. (-)-Baclofen protects guinea-pigs from the anaphylactic bronchospasm induced in sensitized animals by an ovalbumin aerosol and from that induced by aerosols of histamine and PGF2 alpha. Moreover (-)-baclofen reduces the TXA2 and TXB2 output induced by ovalbumin from isolated sensitized guinea-pig lungs. On the other hand (-)-baclofen does not show antihistaminic, anticholinergic or antiprostaglandinic action on isolated tracheal preparations. It is concluded that baclofen can provide protection from bronchial hyperreactivity possibly through a modulation of autonomic nervous system activity.

Topics: Acetylcholine; Anaphylaxis; Animals; Baclofen; Bronchial Spasm; Dinoprost; Guinea Pigs; Histamine Antagonists; Lung; Male; Prostaglandins F; Thromboxane A2; Thromboxane B2

Clenbuterol, an adrenergic beta-mimetic agent free of cardiostimulant effects, prevents the release of histamine from isolated rat mast cells. We studied its anti-anaphylactic activity in guinea-pigs and compared it with that of isoprenaline. At doses inactive against the bronchoconstriction caused by 5HT, clenbuterol (3 micrograms/kg) and isoprenaline (0.1-0.3 micrograms/kg) prevented the bronchoconstriction due to 1 mg/kg ovalbumin infused into passively sensitized animals. Clenbuterol and isoprenaline (0.5-1 microM) inhibited by 40% the contractions of superfused parenchyma lung strips from actively sensitized animals, stimulated with 0.3, 1 and 10 micrograms of ovalbumin. When strips from passively sensitized animals were challenged in the organ bath, clenbuterol and isoprenaline (0.01 microM) reduced by 50% the contraction triggered by 10 micrograms/ml of ovalbumin. These concentrations of clenbuterol were ineffective against contractions caused by acetylcholine. Clenbuterol and isoprenaline (0.001-0.01 microM) inhibited the release of histamine and of thromboxane A2 triggered by ovalbumin (0.1, 1 and 10 micrograms) injected into isolated lungs from actively sensitized guinea-pigs indicating that the anti-anaphylactic properties of clenbuterol are independent from its smooth muscle relaxing activity.

Topics: Acetylcholine; Anaphylaxis; Animals; Bronchi; Clenbuterol; Ethanolamines; Female; Guinea Pigs; Histamine Release; Immunization; Immunization, Passive; Isoproterenol; Lung; Male; Muscle Contraction; Muscle Relaxation; Muscle, Smooth; Serotonin; Thromboxane A2

Thromboxane A2 (rabbit aorta-contracting substance) is a proaggregatory vasoconstrictive, oxygenated metabolite of arachidonic acid which was originally discovered in guinea pig lung perfusates during antigen-induced anaphylaxis. The specific stimuli which activate synthesis and the cellular source in the lung remain undefined. In order to study pulmonary thromboxane A2 (TXA2) synthesis, a cultured lung cell model has been used. Monolayer cultures of human diploid embryonic lung fibroblast (WI-38) metabolized exogenously supplied [14C]arachidonic acid to TXA2 as well as prostaglandin E2. Both were unequivocally identified by gas chromatography/mass spectrometry. Cellular phospholipids were labeled by preincubating cultures overnight with [14C]arachidonic acid. Release of thromboxane A2 into the culture fluid from these prelabeled cultures was stimulated by two phospholipase activating agents, mellitin and the calcium ionophore A23187. The lung cells also released TXA2 and prostaglandin in a dose-dependent fashion when treated with thrombin but not when exposed to trypsin. Bradykinin, an anaphylactic mediator in vivo, was a potent TXA2 releasing agent in this in vitro system whereas histamine was inactive. In addition, anaphylactic shock perfusates from guinea pig lung were shown to contain a factor (other than bradykinin) which activates fibroblasts TXA2 synthesis in these cultured lung cells. These experiments indicate that the lung fibroblast is probably a source of pulmonary thromboxane in vivo and that the cultured lung cell system described here is a useful model for defining the complex interactions of mediators of anaphylaxis and asthma.

Topics: Anaphylaxis; Animals; Arachidonic Acid; Arachidonic Acids; Carbon Radioisotopes; Cell Line; Dinoprostone; Female; Fibroblasts; Guinea Pigs; Humans; Lipid Metabolism; Lung; Prostaglandins E; Thromboxane A2; Thromboxanes

Antigen challenge of passively sensitized chopped human lung resulted in the generation of several arachidonic acid cyclooxygenase metabolites (AACM): thromboxane A2 (TxA2) as measured by its stable metabolite TxB2, prostaglandin D2 (PgD2), prostacyclin (PgI2) as measured by its stable metabolite 6-keto-PgF1 alpha, prostaglandin F2 alpha (PgF2 alpha), and prostaglandin E (PgE). The kinetics of AACM release after antigen challenge paralleled histamine release. All AACM were released in an antigen dose-dependent manner and reached maximal release at antigen concentrations lower than those required for maximal histamine release. Quantitatively, of the AACM measured, PgD2 and PgI2 were found to predominate in anaphylactic reactions of human lung parenchyma. Generation of PgD2 and PgI2 were 3- to 7-fold greater than that of other AACM measured. Thromboxane B2 was generated in quantities comparable to PgE and PgF2 alpha. Studies were designed to test the hypothesis that lung smooth muscle contraction per se can account for the generated AACM that are released during anaphylaxis of the lung. The studies compared antigen-induced AACM generation with methacholine-induced (10(-4) M) AACM generation. The failure to confirm this hypothesis was especially evident for PgD2 where release was dependent on mast cell activation. Thromboxane A2, PgD2, and PgI2 have been reported to have potent effects on smooth muscle. Our data suggested that these AACM are generated in such sufficient quantities that they may function in important aspects of the modulation of hypersensitivity responses in human lungs.

Topics: Anaphylaxis; Antigens; Arachidonic Acid; Arachidonic Acids; Dinoprost; Epoprostenol; Histamine Release; Humans; In Vitro Techniques; Lung; Mast Cells; Methacholine Compounds; Muscle Contraction; Muscle, Smooth; Prostaglandins; Prostaglandins D; Prostaglandins E; Prostaglandins F; Thromboxane A2; Thromboxanes

In the dog, different cardiorespiratory reactions were identified in two types of anaphylactic shock and in C5a-AT (anaphylatoxin)-induced shock. All three types had in common a portal blood pooling with consequent decrease in the venous return, cardiac output, and arterial pressure. In anaphylaxis (a) of the first type, at a low titer of hemagglutinating antibodies, the latent period was 68 s and heart and lung function was unchanged. In the second type, at high titer, the latency was 19 s and pulmonary hypertension and decreased heart contractility occurred. After AT injection pulmonary hypertension appeared with tachypnea and unchanged heart function. Tachyphylaxis, but not cross-over tachyphylaxis against the anaphylactic agent and AT was observed in dogs and isolated guinea pig lungs. AT induced a transient release and a, a prolonged release of histamine, prostaglandins (PGs), and thromboxane A2 and endoperoxides from guinea pig lungs. SRS-A was released only in a. Indomethacin inhibited AT-induced release of PGs in guinea-pig lungs and AT-induced hypotension in the dog though it did not prevent the drop in cardiac output. These model studies suggest that different patterns of clinical a. can occur, depending on the type of antibodies and/or mediators involved.

Topics: Anaphylatoxins; Anaphylaxis; Animals; Blood Pressure; Cardiac Output; Guinea Pigs; Heart Rate; Hemodynamics; Histamine Release; Indomethacin; Lung; Male; Myocardial Contraction; Peptides; Prostaglandin Endoperoxides; Prostaglandins; Respiration; SRS-A; Thromboxane A2

Topics: Airway Resistance; Anaphylaxis; Animals; Arachidonic Acids; Benzothiazoles; Bronchodilator Agents; Guinea Pigs; Histamine Release; Humans; In Vitro Techniques; Lung; Male; Muscle Contraction; Muscle, Smooth; Piperazines; Rabbits; Thiazoles; Thromboxane A2; Trachea

Topics: Anaphylaxis; Animals; Aorta; Biological Assay; Bradykinin; Lung; Muscle, Smooth; Ovalbumin; Rabbits; Rats; Species Specificity; Thromboxane A2; Thromboxanes; Vasoconstriction

Fragments of chopped lung from indomethacin treated guinea-pigs had an anti-aggregating effect when added to human platelet rich plasma (PRP), probably due to the production of prostacyclin (PGI2) since the effect was inhibited by 15-hydroperoxy arachidonic acid (15-HPAA, 10 micrograms ml(-1)). Both 15-HPAA (1-20 micrograms ml(-1) min (-1)) and 13-hydroperoxy linoleic acid (13-HPLA, 20 micrograms ml(-1) min(-1)) caused a marked enhancement of the anaphylactic release of histamine, slow-reacting substance of anaphylaxis (SRS-A) and rabbit aorta contracting substance (RCS) from guinea-pig isolated perfused lungs. This enhancement was not reversed by the concomitant infusion of either PGI2 (5 micrograms ml(-1) min (-1)) or 6-oxo-prostaglandin F1alpha (6-oxo-PGF1alpha, 5 micrograms ml(-1) min(-1)). Anaphylactic release of histamine and SRS-A from guinea-pig perfused lungs was not inhibited by PGI2 (10 ng - 10 microgram ml(-1) min(-1)) but was inhibited by PGE2 (5 and 10 micrograms ml(-1) min (-1)). Antiserum raised to 5,6-dihydro prostacyclin (PGI1) in rabbits, which also binds PGI2, had no effect on the release of anaphylactic mediators. The fatty acid hydroperoxides may enhance mediator release either indirectly by augmenting thromboxane production or by a direct effect on sensitized cells. Further experiments to distinguish between these alternatives are described in the accompanying paper (27).

Topics: Anaphylaxis; Animals; Antigens; Arachidonic Acids; Epoprostenol; Guinea Pigs; Histamine Release; Humans; Immune Sera; Indomethacin; Linoleic Acids; Lung; Male; Perfusion; Platelet Aggregation; Prostaglandins E; Prostaglandins F; SRS-A; Thromboxane A2

The antigen-antibody union initiates the release of mediators; the reactions and interactions of these mediators in the lung appear to include negative feedback mechanisms. During anaphylactic bronchoconstriction catecholamines are released from the adrenal medulla. These act as physiological antagonists and tend to reverse the bronchoconstriction. In guinea-pig and human lung fragments, catecholamines and PGs increase cyclic AMP levels and inhibit the release of histamine, SRS-A and ECF-A following antigen challenge. EFC-A is chemotactic to eosinophils which contain arylsulphatase which destroys SRS-A. Aanphylactic bronchoconstriction seems to be a defense mechanism to limit further inhalation of antigen by the animal. It then seems that a series of negative feedback mechanisms may be triggered to terminate and reverse the bronchoconstriction and prevent further release of mediators.

Topics: Anaphylaxis; Animals; Bradykinin; Bronchi; Catecholamines; Cattle; Guinea Pigs; Histamine Release; Humans; Kallikreins; Lung; Prostaglandins E; Prostaglandins F; SRS-A; Thromboxane A2

During anaphylactic reactions there are released thromboxane A2 and/or prostaglandin-like substances from perfused guinea pig lungs and from incubated fragments of guinea pig mesentery. Prostaglandin-like substances appear also in mixed venous blood of anaesthetized cats following an intravenous injection of rabbit blood. These release reactions are reduced or abolished both by indomethacin and by hydrocortisone.

Topics: Anaphylaxis; Animals; Cats; Glucocorticoids; Guinea Pigs; Hydrocortisone; In Vitro Techniques; Indomethacin; Lung; Mesentery; Prostaglandins; Thromboxane A2