burimamide and Anaphylaxis

The effects of H2-blocking agents and the H2 receptor agonist, 4-methylhistamine, on the severity of anaphylactic reactions were studied in the guinea pig in vivo. The increase in gas volume of the lungs 90 sec after intravenous infusion of ovalbumin in animals immunized previously by intraperitoneal ovalbumin injection was used as an index of the severity of the reaction in vivo. The H2 receptor antagonists burimamide (1.0 and 3.0 mg per kg) and metiamide (3 mg per kg) significantly increased the severity of the reaction but did not significantly alter the effects of subcutaneous histamine. Neither 3 nor 30 mg of cimetidine per kg increased the severity of the reaction, and the higher dose significantly blunted the response to subcutaneous histamine. The H2 receptor agonist, 4-methylhistamine, significantly diminished the severity of the reation. These experiments demonstrate that H2 receptor stimulation may act to limit the severity of the anaphylactic reactions in vivo.

Topics: Anaphylaxis; Animals; Burimamide; Cimetidine; Feedback; Guinea Pigs; Lung; Lung Volume Measurements; Male; Methylhistamines; Metiamide; Receptors, Histamine; Receptors, Histamine H2

Histamine and one of its major metabolites, imidazoleacetic acid, were selectively chemotactic for guinea pig eosinophils, whereas L-histidine, 1,4-methylimidazoleacetic acid, 1,4-methylhistamine and N-acetylhistamine were inactive. The response to histamine was unaffected by concentrations of eosinophils of between 30 and greater than 90% but it was abrogated by preincubation of the cells with histamine prior to assay (self-deactivation). Eosinophilotaxis was also inhibited by H1-(mepyramine-) and H2-)burimamide)-receptor antagonists at high doses (10(-3)m), although at lower concentrations (10(-5) M) inhibition was principally associated with burimamide. The human tetrapeptide, alanine-glycine-serine-glutamic acid, and the analogue, valine-glycine-aspartic acid-glutamic acid, were inactive whereas alanine-glycine-serine-glutamic acid was chemotactic for the guinea pig eosinophil. These results support the concept that the tissue accumulation of eosinophils following anaphylaxis depends on a complex interaction of factors, which in part may be mediated by H2 receptors on the target cells. There may be species differences in the composition of ECF-A.

Topics: Alanine; Anaphylaxis; Animals; Burimamide; Chemotaxis, Leukocyte; Dose-Response Relationship, Immunologic; Eosinophils; Female; Glutamates; Guinea Pigs; Histamine; Histamine H1 Antagonists; Histamine H2 Antagonists; Histidine; Imidazoles; Male; Methylhistamines; Oligopeptides; Pyrilamine; Valine

Topics: Amine Oxidase (Copper-Containing); Anaphylaxis; Animals; Burimamide; Cyclic AMP; Feedback; Guinea Pigs; Histamine; Lung; Metiamide; Pyridines; Pyrilamine; Thiourea

The effects of burimamide, an H2-antihistamine, on the anaphylactic reaction in the skin of ovalbumin-sensitized guinea pigs were studied in vitro. Burimamide enhanced the concentration of histamine in the supernatant fraction of antigen-challenged sensitized guinea-pig skin in a dose-related way, but did not alter the concentration of residual histamine in the skin after antigen challenge. The enhanced histamine concentration in the supernatant was not due to increased histamine synthesis by the target cells during the reaction because the increase was not inhibited by a histidine decarboxylase inhibitor, Brocresine. In further experiments it was shown that guinea-pig skin possesses potent histamine degrading enzyme activity which is inhibited by burimamide. We suggest that inhibition of these degrading enzymes leads to the increase in histamine concentration in the presence of burimamide.

Topics: Anaphylaxis; Animals; Brocresine; Burimamide; Guinea Pigs; Histamine; Histidine Decarboxylase; In Vitro Techniques; Male; Skin; Thiourea

A four-fold transient rise in c-AMP levels was seen when sensitized guinea-pig lungs were challenged with antigen in vitro. This rise in c-AMP also occurred in vivo and was shown to be due to release of Prostaglandin E2. This conclusion is supported by the finding that inhibitors of prostaglandin synthesis (Indomethacin and Poly phloretin phosphate) prevent the rise in c-AMP while neither ICI 74, 917, an inhibitor of histamine release, nor antihistamines had any effect on the c-AMP levels.

Topics: Anaphylaxis; Animals; Burimamide; Cyclic AMP; Guinea Pigs; Histamine; Immunization; Indomethacin; Isoproterenol; Lung; Ovalbumin; Polyphloretin Phosphate; Propranolol; Prostaglandins E; Prostaglandins F; Pyrilamine; Serotonin