Inhibition of airway hyperreactivity, edema, and lung cell infiltration by compound U-83836E in sensitized guinea pigs.
Sensitized guinea pigs were used to assess the effect of treatment with the compound U-83836E ((-)-2-[[4-(2,6-di-1-pyrrolidinyl-4-pyrimidinyl)-1-piperazinyl]methyl]-3 ,4-dihydro-2,5,7,8-tetramethyl-2H--benzopyran-6-ol, dihydrochloride) on the antigen-induced late-phase (16 h) airway hyperreactivity, increase in inflammatory cell number, edema, and release of inflammatory mediators in the bronchoalveolar lavage (BAL) fluid. After antigen challenge, an increase of the in vitro reactivity of the trachea and upper bronchi to acetylcholine and histamine and an increase in the number of leukocytes in the BAL fluid, mainly eosinophils and mononuclear cells, were observed. The concentrations of proteins, histamine, and PGE2 in the BAL fluid were also significantly increased by 53, 57, and 216%, respectively, after antigen challenge. Treatment with U-83836E (10 mg/kg) given i.p. 17 and 3 h before and 6 h after antigen challenge inhibited by approximately 80% the total cell number in the airways and the BAL fluid protein content. Moreover, this treatment totally inhibited airway hyperreactivity. Histamine and PGE2 levels in the BAL fluid were not significantly affected by U-83836E treatment. These results indicate that U-83836E is effective against some of the characteristic features of asthma in ovalbumin-sensitized guinea pigs.
Department of Pharmacology, Medical School, University of Sherbrooke, QC, Canada.
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D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D018927:Anti-Asthmatic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology* / Q000627:therapeutic use; D016535:Bronchial Hyperreactivity / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D002634:Chemotaxis, Leukocyte / Q000187:drug effects*; D002839:Chromans / Q000494:pharmacology* / Q000627:therapeutic use; D015232:Dinoprostone / Q000378:metabolism; D004487:Edema / Q000139:chemically induced / Q000517:prevention & control*; D004804:Eosinophils / Q000187:drug effects; D006168:Guinea Pigs; D006632:Histamine / Q000737:chemistry; D006636:Histamine Release / Q000187:drug effects; D007249:Inflammation / Q000517:prevention & control; D008168:Lung / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D009000:Monocytes / Q000187:drug effects; D010047:Ovalbumin; D010879:Piperazines / Q000494:pharmacology* / Q000627:therapeutic use; D013929:Thromboxane B2 / Q000378:metabolism
D018927:Anti-Asthmatic Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal; D002839:Chromans; D010879:Piperazines; C066382:U 78517F; D013929:Thromboxane B2; D006632:Histamine; D010047:Ovalbumin; D015232:Dinoprostone; D000109:Acetylcholine