metiamide and Anaphylaxis

Topics: Anaphylaxis; Animals; Antigens; Barium; Barium Compounds; Chlorides; Female; Guinea Pigs; Histamine; Histamine H1 Antagonists; In Vitro Techniques; Methysergide; Metiamide; Ovalbumin; Papaverine; Phentolamine; Pulmonary Artery; Vasoconstriction

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

Tracheal smooth muscle (TSM) from an ovalbumin sensitized canine model of allergic asthma showed hypersensitivity and hyper-reactivity to histamine (H) when compared to that from littermate controls in vitro. Mepyramine abolished H responses in TSM of both groups; it also abolished the allergic response to obalbumin of TSM from sensitized dogs. The H2 receptor agonist, 4-methyl histamine (4-MH) caused small dose-related decreases in H contractures but had no effect on carbachol- or K+-induced tension. Metiamide, an H2 antagonist, did not enhance the H contracture, suggesting the 4-MH may not be exerting a relaxant effect since H2 receptors were absent. The maximum H-induced isometric tension was potentiated when the sensitized and control muscle strips were pre-equilibrated with 4-MH. These observations are consistent with the presence in canine TSM of H1 but not relaxant H2 receptors, the release of endogenous H to the tissue during the antigen-antibody reaction, and the competition of H and 4-MH for the H1 receptors. Experiments with specific blockers also indicated that in this model the only transmitter found in the ovalbumin-induced allergic bronchospasm was histamine.

Topics: Airway Resistance; Anaphylaxis; Animals; Asthma; Dogs; Histamine; In Vitro Techniques; Methylhistamines; Metiamide; Muscle Contraction; Muscle, Smooth; Ovalbumin; Pyrilamine; Receptors, Histamine H2; Trachea

1 Isolated lung parenchymal strips of the dog contracted in response to histamine > carbachol > prostaglandin F(2alpha) (PGF(2alpha)) > bradykinin (Bk) > 5-hydroxytryptamine (5-HT). The order of the relative activity of these agents on the tracheobronchial smooth muscles (TBSM) was carbachol > 5-HT > histamine; PGF(2alpha) and Bk were inactive. Thus there are marked differences in the responsiveness of the smooth muscle of central (trachea and bronchus) and peripheral (lung strip) airways to autonomic and autacoid agents.2 Lung strips and TBSM partially contracted by carbachol, histamine or horse plasma, were relaxed by isoprenaline, PGE(1) and PGE(2).3 Lung strips from dogs sensitized to horse-plasma contracted in response to antigen (Schultz-Dale anaphylactic reaction). Tachyphylaxis or desensitization to subsequent antigen challenge was invariably observed; it was followed after 1 to 2 h of rest by partial recovery of the anaphylactic response.4 Mepyramine selectively antagonized responses to histamine without altering responses to carbachol and antigen.5 Metiamide, an H(2)-receptor antagonist, did not influence responses to histamine, carbachol or horse plasma.6 Indomethacin was found to be ineffective as an inhibitor of the Schultz-Dale anaphylactic reaction.7 The results showed the presence of H(1)-histamine receptors mediating constriction in the peripheral airways of the dog. Histamine and PGF(2alpha) appear to have no important role in the anaphylactic reaction in this tissue. The involvement of slow reacting substance of anaphylaxis (SRS-A) and endoperoxides (thromboxanes) in allergic reactions of canine lung is strongly suggested.

Topics: Anaphylaxis; Animals; Asthma; Autacoids; Disease Models, Animal; Dogs; Female; Histamine H1 Antagonists; In Vitro Techniques; Indomethacin; Lung; Male; Metiamide; Pyrilamine

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: Anaphylaxis; Animals; Female; In Vitro Techniques; Lung; Male; Metiamide; Mice; Ovalbumin; Pyrilamine; Receptors, Histamine; Receptors, Histamine H2

Topics: Anaphylaxis; Animals; Brompheniramine; Chromones; Dose-Response Relationship, Drug; Ethers; Female; Guinea Pigs; Histamine; Indomethacin; Lung; Male; Metiamide; Ovalbumin; Receptors, Histamine H1

Chopped lung and isolated leukocytes of calves sensitized to horse plasma release histamine when incubated with the antigen. Low concentrations (10(-9) and 10(-8) M) of exogenous histamine enhanced both spontaneous and antigen-induced histamine release. The enhancement of antigen-induced histamine release was inhibited by metiamide but not by mepyramine, whereas the enhancement of spontaneous histamine release was not significantly affected by either histamine antagonist. At higher concentrations of exogenous histamine (10(-6) to 10(-4) M), uptake and metabolism significantly interfered with the method. These results indicate the existence in bovine lung and leukocyte of a positive feedback mechanism which regulates histamine release via an H2-receptor. This is in direct contrast to the reported situation in the human leukocyte, and suggests that histamine fulfils an important role in the intrinsic control of allergic reactions in cattle.

Topics: Anaphylaxis; Animals; Cattle; Granulocytes; Histamine; Histamine Release; In Vitro Techniques; Leukocytes; Lung; Male; Metiamide; Pyrilamine; Receptors, Histamine; Receptors, Histamine H2

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

Topics: Anaphylaxis; Animals; Cyclic AMP; Cyclic GMP; Guinea Pigs; Histamine Release; In Vitro Techniques; Kinetics; Lung; Male; Mast Cells; Metiamide; Perfusion; Prostaglandins F

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

The anaphylactic contraction (Schultz-Dale response) of the isolated uterus from actively sensitized rats was partially suppressed by methysergide, 1.5 mug/ml. Although the inhibitory effect of indomethacin, 3.5 mug/ml, was only slight, the combination of indomethacin and methysergide abolished the response almost completely. These observations indicate that, although serotonin must be the primary mediator of tha anaphylactic uterine response, prostaglandin is also involved. Metiamide, a histamine H2-receptor antagonist, 10 mug/ml, did not affect the anaphylactic response, suggesting that histamine was not released in amounts sufficient to counteract the uterine contracting mediators.

Topics: Anaphylaxis; Animals; Female; Histamine; Indomethacin; Methysergide; Metiamide; Rats; Rats, Inbred Strains; Time Factors; Uterine Contraction

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

Topics: Anaphylaxis; Animals; Histamine; Histamine Release; Humans; Hypersensitivity, Immediate; Immunoglobulin E; Lung; Macaca mulatta; Male; Metiamide; Rats; Receptors, Drug; Skin; SRS-A