Changes in bronchial anaphylactic reactivity induced in guinea-pigs by long-term treatment with histamine H2-agents.
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.
D000707:Anaphylaxis / Q000503:physiopathology*; D000818:Animals; D001980:Bronchi / Q000187:drug effects* / Q000276:immunology / Q000503:physiopathology; D002927:Cimetidine / Q000494:pharmacology; D017259:Dimaprit / Q000031:analogs & derivatives; D005260:Female; D006168:Guinea Pigs; D006635:Histamine H2 Antagonists / Q000494:pharmacology*; D006636:Histamine Release / Q000187:drug effects; D007073:Immunoglobulin E / Q000032:analysis; D007074:Immunoglobulin G / Q000032:analysis; D066298:In Vitro Techniques; D008168:Lung / Q000378:metabolism; D008297:Male; D010047:Ovalbumin / Q000276:immunology; D010323:Passive Cutaneous Anaphylaxis / Q000187:drug effects; D012129:Respiratory Function Tests; D013890:Thiourea / Q000494:pharmacology
D006635:Histamine H2 Antagonists; D007074:Immunoglobulin G; C024535:SK&F 91488; D007073:Immunoglobulin E; D002927:Cimetidine; D010047:Ovalbumin; D013890:Thiourea; D017259:Dimaprit