thiourea and Anaphylaxis

Topics: Adult; Anaphylaxis; Cresols; Dermatitis, Allergic Contact; Disinfectants; Female; Fungicides, Industrial; Humans; Thiourea; Urticaria; Xylenes

The effects of histamine and of H1- and H2-receptor agonists on the response to specific antigen were studied in isolated hearts taken from actively sensitized guinea-pigs. Histamine and H2-receptor agonists (dimaprit, impromidine) dose-dependently decrease the positive chronotropic and inotropic effects, and the severity of arrhythmias evoked by the challenge of sensitized hearts with specific antigen. Nordimaprit and the selective H1-receptor agonist 2-pyridyl-ethyl-amine (2-PEA) did not modify the patterns of cardiac anaphylaxis. The positive inotropic and chronotropic responses of the isolated heart to exogenous histamine appear to be partly reduced in the presence of dimaprit. The H2-receptor agonists decrease the amount of histamine released during cardiac anaphylaxis which is increased by cimetidine, while nordimaprit and PEA were ineffective, indicating an inhibitory function afforded by H2-receptors in cardiac anaphylaxis.

Topics: Anaphylaxis; Animals; Cimetidine; Dimaprit; Female; Guinea Pigs; Heart; Heart Rate; Histamine; Histamine H1 Antagonists; Histamine H2 Antagonists; In Vitro Techniques; Male; Myocardial Contraction; Pyridines; Thiourea

Guinea-pigs were sensitized to ovalbumin (OA) by immunization regimens chosen to cause antigen-induced bronchial anaphylactic responses mediated mainly either by IgE-like antibodies or by IgG1-like antibodies. Treatment of the IgE-producing animals for three weeks with the histamine H2-receptor antagonist cimetidine (1 mg kg-1 i.p. once a day) or with the H2-agonist dimaprit (0.1, 1.0, or 10 mg kg-1 i.p. once a day) led to a significantly reduced bronchial response capacity compared with that of the saline-treated controls challenged intravenously with antigen one week after the end of treatment. The changes were biphasic and not strictly dose-dependent. In contrast, acute treatment of immunized animals with a single dose of cimetidine (10 or 30 mg kg-1 i.v.) or dimaprit (1 or 10 mg kg-1 i.v.) 2 min before challenge with OA did not significantly affect the bronchial anaphylactic response. However, long-term treatment with cimetidine (10 mg kg-1) or the dimaprit analogue, S-[4-(N, N-dimethylamino)-butyl] isothiourea (SKF Compound 91488) (1 mg kg-1), which is reported not to activate H2-receptors, had no effect on the response capacity. Treatment with cimetidine (1 mg kg-1) or dimaprit (1 mg kg-1) did not influence the response capacity to antigen challenge in IgG1- type animals. Dimaprit (1 mg kg-1) did not affect the responsiveness to intravenous provocation with histamine in 'IgE-type' animals. Antigen-induced release of histamine from chopped lung tissue in vitro was not significantly affected in 'IgE-type' animals treated with cimetidine (1 mg kg-1) or dimaprit (1 mg kg-1). Treatment of immunized animals with cimetidine or dimaprit one week before and one week after a booster injection of antigen also led to reduced response capacity compared with that of saline-treated controls. However, the serum levels of IgE-like homocytotropic antibodies of these animals were not reduced; on the contrary, those of IgG1-antibody were increased in dimaprit-treated animals. These data show that intermittent treatment with histamine H2-agents reduces reagin-mediated anaphylactic response capacity in vivo in actively sensitized guinea-pigs by an as yet undefined mode of action.

Topics: Anaphylaxis; Animals; Bronchi; Cimetidine; Dimaprit; Female; Guinea Pigs; Histamine H2 Antagonists; Histamine Release; Immunoglobulin E; Immunoglobulin G; In Vitro Techniques; Lung; Male; Ovalbumin; Passive Cutaneous Anaphylaxis; Respiratory Function Tests; Thiourea

The established Konzett-Rossler bronchorespiratory model has been combined with a unique ovalbumin sensitization procedure to give a novel method to measure anaphylaxis in the anaesthetized guinea-pig. Following antigen challenge, up to eight equal bronchoconstrictor responses to the same dose can be generated from a single animal over a 120 min period. Total inhibition of the anaphylactic response can be elicited by four different classes of compound, namely salbutamol, mepyramine, theophylline and dimaprit. Cromoglycate failed to cause any inhibition. The method is discussed with particular reference to the antigen sensitization procedure, which differs substantially from other regimens previously employed and gives rise to heat labile antibody.

Topics: Albuterol; Anaphylaxis; Animals; Antibodies; Cromolyn Sodium; Dimaprit; Guinea Pigs; Male; Pyrilamine; Theophylline; Thiourea

Two selective H2-histamine agonists, dimaprit and impromidine, have been tested for their action on histamine release from human basophils and rat mast cells. IgE-mediated basophil histamine release was inhibited by stimulation of histamine H2-receptors. However, differences between the actions of both dimaprit and impromidine were noticed. Both impromidine and dimaprit had no specific effect on 48/80-induced histamine release from rat mast cells, although the latter in higher concentrations either slightly increased spontaneous histamine release or non-specifically inhibited compound 48/80-induced release. The results are consistent with the view that activation of adenylate cyclase via H2-histamine receptors might be an important regulatory mechanism of histamine release from human basophils but not from rat mast cells.

Topics: Allergens; Anaphylaxis; Basophils; Dimaprit; Guanidines; Histamine Release; Humans; Imidazoles; Impromidine; In Vitro Techniques; Mast Cells; p-Methoxy-N-methylphenethylamine; Receptors, Histamine; Receptors, Histamine H2; Thiourea

Pentobarbital-anesthetized and spontaneously breathing, bovine albumin (BA)-sensitized adult domestic fowl showed acute systemic anaphylaxis to IV injection of antigen (BA), which was characterized by arterial hypotension, central venous hypertension, and bradycardia. Large doses of pyrilamine maleate (/1-receptor antagonist) partially inhibited acute systemic anaphylaxis. On the other hand, metiamide (a specific H2-antagonist) and propranolol (beta-adrenergic antagonist) markedly enhanced the anaphylactic response. Terbutaline (beta 2-agonist), dimaprit (a highly selective H2-agonist), and compound FPL 55712 (a slow-reacting substance of anaphylaxis receptor antagonist) either significantly inhibited or reversed the anaphylactic response. Cimetidine (a newer H2-antagonist) enhanced only central venous pressor response to BA. This investigation appears to suggest a minor role of histamine and a major role of slow-reacting substance of anaphylaxis as chemical mediatiors of anaphylaxis. A protective role of beta 2-adrenergic and H2-histaminergic receptors seem to operate in immediate hypersensitivity reactions in adult domestic fowl.

Topics: Anaphylaxis; Animals; Blood Pressure; Carotid Arteries; Chickens; Chromones; Cimetidine; Dimaprit; Ethers; Heart Rate; Metiamide; Poultry Diseases; Propranolol; Pyrilamine; Receptors, Adrenergic; Receptors, Adrenergic, beta; Receptors, Histamine; Receptors, Histamine H2; Terbutaline; Thiourea

Theoretically, histamine H2 antagonists could aggravate allergic bronchoconstriction (1) by increasing mediator release, and (2) by blocking histamine-induced bronchodilatation. We measured dynamic compliance, subdivisions of lung volume, and mortality in immunized guinea pigs after parenteral administration of antigen, with and without pretreatment with the H2-blocking agents cimetidine and metiamide. Administration of antigen caused significant mortality as well as decreases in dynamic compliance, total lung capacity, and vital capacity and increases in functional residual capacity. The prior administration of cimetidine or metiamide did not protect against or enhance these effects of antigen challenge.

Topics: Anaphylaxis; Animals; Cimetidine; Functional Residual Capacity; Guanidines; Guinea Pigs; Lung; Lung Compliance; Metiamide; Thiourea; Total Lung Capacity; Vital Capacity

Topics: Anaphylaxis; Animals; Gastric Mucosa; Guinea Pigs; Metiamide; Thiourea

The effects of metiamide and of four H1 receptor blocking agents (mepyramine, promethazine, clemastine and ketotifene) on anaphylactic reaction were studied in the guinea-pig. The H1 blockers conferred partial protection which shows that with the experimental protocol utilized (challenge injection with high doses of antigen), histamine plays a lesser role than other mediators released or synthesized. Metiamide (30.0 mg/kg i.v.) noticeably enhanced the increase in pulmonary resistance observed during anaphylactic reaction and reduced the protective effect of the H1 antagonists on this parameter and on histamine release. These effects might be explained by an inhibition - at least partial - of the negative feed-back mechanism through which histamine controls its own release, or by a specific action of metiamide in high doses. The transient tachycardia initially observed in anaphylactic shock is partly related to stimulation of cardiac H2 receptors by the histamine released, since it is suppressed by metiamide.

Topics: Airway Resistance; Anaphylaxis; Animals; Blood Pressure; Bronchial Spasm; Guinea Pigs; Heart Rate; Histamine; Histamine H1 Antagonists; Histamine Release; Lung; Male; Metiamide; Thiourea

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

Topics: Anaphylaxis; Animals; Guinea Pigs; Lung Volume Measurements; Metiamide; 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

Topics: Analysis of Variance; Anaphylaxis; Animals; Antigen-Antibody Reactions; Benzyl Compounds; Carbon Radioisotopes; Cyclic AMP; Cyclic GMP; Ethylenediamines; Guinea Pigs; Histamine; Histamine H1 Antagonists; Humans; Imidazoles; In Vitro Techniques; Iodine Radioisotopes; Lung; Ovalbumin; Pyridines; Rabbits; Radioimmunoassay; Thiourea; Tritium

1. Anaphylaxis was induced in the isolated heart of the guinea-pig in the presence of burimamide at concentrations of 4 x 10(-5)M and 2.7 x 10(-4)M.2. Burimamide did not affect the immunological release of histamine; however, it selectively antagonized the positive inotropic and chronotropic effects of released histamine. The antagonism of the positive chronotropic effect was concentration-dependent.3. Neither the negative dromotropic effect nor the decrease in coronary flow rate occurring during anaphylaxis were inhibited by burimamide.4. The results are in agreement with the double histamine receptor theory and suggest that, in the heart of the guinea-pig, H(2)-receptors are involved in the positive inotropic and chronotropic effects of released histamine, and H(1)-receptors in the negative dromotropic effect.

Topics: Anaphylaxis; Animals; Antigens; Electrocardiography; Guinea Pigs; Heart; Heart Rate; Histamine H1 Antagonists; Histamine Release; Imidazoles; In Vitro Techniques; Ovalbumin; Receptors, Drug; Thiourea; Time Factors; Transducers

Topics: Anaphylaxis; Drug-Related Side Effects and Adverse Reactions; Histamine; Psychoses, Substance-Induced; Shock; Thiourea; Thyroid Gland

Topics: Anaphylaxis; Hypersensitivity; Immune System Diseases; Thiourea

Topics: Anaphylaxis; Hypersensitivity; Immune System Diseases; Shock; Thiourea