Histamine and leukotriene-independent guinea-pig anaphylactic shock unaccounted for by Paf-acether. 1985

A Detsouli, and J Lefort, and B B Vargaftig

Ovalbumin induced dose-dependent contractions of lung parenchyma strips from sensitized guinea-pigs, whereas Paf-acether (1-alkyl-2-acetyl-sn-glycero-3-phosphoryl choline), a potential mediator of immediate hypersensitivity, induced a single contraction, followed by specific desensitization to a second exposure. Lung strips desensitized to Paf-acether contracted to ovalbumin as did non-desensitized controls, even in the presence of inhibitors of other mediators of anaphylaxis. Contractions by Paf-acether and by ovalbumin were reduced by nordihydroguaiaretic acid (NDGA) and by the phospholipase A2 inhibitor p-bromophenacyl bromide (0.1-0.3 mM). Three other anti-lipoxygenase agents (diethylcarbamazine, 5 mM; eicosatetraynoic acid and BW755c, 0.1 mM), reduced the contractions by ovalbumin but also those due to acetylcholine, indicating non-specific effects. Neither the anti-allergic compound sodium cromoglycate (3 mM) nor the anti-leukotriene agent, FPL 55712 (0.01 mM), inhibited the contractions by ovalbumin or by Paf-acether. A sensitized strip stimulated with ovalbumin released substances which contracted a non-sensitized strip mounted in the same organ bath. The contractions of the non-sensitized strip were abolished by FPL 55712 (0.01 mM), by NDGA and BW755c, (0.1 mM), whereas those of the sensitized one were unaffected. Leukotrienes are formed by the lung strips during shock but alone, they do not explain the contractile activity. The intravenous administration of ovalbumin (1 mg kg-1) led to bronchoconstriction and thrombocytopenia, which were not modified by the anti-leukotriene substance FPL 55712 nor by aspirin. Bronchoconstriction was suppressed if FPL 55712 was used in combination with aspirin (20 mg kg-1), mepyramine and methysergide (200 micrograms kg-1 of either). Pretreatment of the guinea-pigs with propranolol reduced this inhibition to approximately 60%. In no instance was thrombocytopenia prevented. In vitro contractions of the actively sensitized lung strip are not fully accounted for by histamine, FPL 55712-inhibitable leukotrienes or Paf-acether, whereas in systemic anaphylaxis histamine and leukotrienes (inhibited respectively by mepyramine and by FPL 55712) have a significant role.

UI MeSH Term Description Entries
D008168 Lung Either of the pair of organs occupying the cavity of the thorax that effect the aeration of the blood. Lungs
D008297 Male Males
D009119 Muscle Contraction A process leading to shortening and/or development of tension in muscle tissue. Muscle contraction occurs by a sliding filament mechanism whereby actin filaments slide inward among the myosin filaments. Inotropism,Muscular Contraction,Contraction, Muscle,Contraction, Muscular,Contractions, Muscle,Contractions, Muscular,Inotropisms,Muscle Contractions,Muscular Contractions
D009637 Masoprocol A potent lipoxygenase inhibitor that interferes with arachidonic acid metabolism. The compound also inhibits formyltetrahydrofolate synthetase, carboxylesterase, and cyclooxygenase to a lesser extent. It also serves as an antioxidant in fats and oils. Nordihydroguaiaretic Acid,(R*,S*)-4,4'-(2,3-Dimethylbutane-1,4-diyl)bispyrocatechol,Actinex,Dihydronorguaiaretic Acid,Nordihydroguaiaretic Acid, (R*,S*)-Isomer,meso-Nordihydroguaiaretic Acid,Acid, meso-Nordihydroguaiaretic,meso Nordihydroguaiaretic Acid
D010972 Platelet Activating Factor A phospholipid derivative formed by PLATELETS; BASOPHILS; NEUTROPHILS; MONOCYTES; and MACROPHAGES. It is a potent platelet aggregating agent and inducer of systemic anaphylactic symptoms, including HYPOTENSION; THROMBOCYTOPENIA; NEUTROPENIA; and BRONCHOCONSTRICTION. AGEPC,Acetyl Glyceryl Ether Phosphorylcholine,PAF-Acether,Phosphorylcholine, Acetyl Glyceryl Ether,1-Alkyl-2-acetyl-sn-glycerophosphocholine,Platelet Aggregating Factor,Platelet Aggregation Enhancing Factor,Platelet-Activating Substance,Thrombocyte Aggregating Activity,1 Alkyl 2 acetyl sn glycerophosphocholine,Aggregating Factor, Platelet,Factor, Platelet Activating,PAF Acether,Platelet Activating Substance
D002396 Catechols A group of 1,2-benzenediols that contain the general formula R-C6H5O2. Pyrocatechols,o-Dihydroxybenzenes,ortho-Dihydroxybenzenes,o Dihydroxybenzenes,ortho Dihydroxybenzenes
D002867 Chromones 1,4-Benzopyrones,Chromone,1,4 Benzopyrones
D005260 Female Females
D006168 Guinea Pigs A common name used for the genus Cavia. The most common species is Cavia porcellus which is the domesticated guinea pig used for pets and biomedical research. Cavia,Cavia porcellus,Guinea Pig,Pig, Guinea,Pigs, Guinea
D006632 Histamine An amine derived by enzymatic decarboxylation of HISTIDINE. It is a powerful stimulant of gastric secretion, a constrictor of bronchial smooth muscle, a vasodilator, and also a centrally acting neurotransmitter. Ceplene,Histamine Dihydrochloride,Histamine Hydrochloride,Peremin

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