Functional identification of epithelial and smooth muscle histamine-dependent relaxing mechanisms in the bovine trachea, but not in bronchi.
Theoretically, the overall effect of histamine on respiratory smooth muscle is the result of a subtle balance of contraction and relaxation. The aim of the study was to identify histamine type 2 (H2) and 3 (H3) receptor-dependent relaxing mechanisms in the contractile elements of the bovine tracheobronchial tree. In bronchial preparations, histamine induced very weak contractions, which were not exacerbated with the H2-antagonist cimetidine. Moreover, precontracted bronchial rings never relaxed in response to cumulative doses of histamine or amthamine (H2-agonist). In intact tracheal preparations, histamine induced strong contractions that were exacerbated by cimetidine (E(max): +17.2+/-6.6%) but not by thioperamide (H3-antagonist). Precontracted tracheal bundles did not relax in response to cumulative doses of the H3-agonist R-alpha-methylhistamine. The tracheal contractile response was higher in denuded compared to intact preparations (11.0+/-1.2 vs. 6.0+/-1.7 g). Cimetidine effect was dramatically potentiated in denuded tracheal strips (+40.0+/-11.7%). It is concluded that the weak response of bovine bronchi to histamine is due to a relative scarcity of H1 receptors on bronchial smooth muscle rather than to H2- or H3-dependent relaxation. In the bovine trachea, the smooth muscle possesses relaxing H2 but no H3 receptors. The epithelium exercises a relaxation, which is independent from H2 and H3 receptors.
Jolly
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Department of Morphology and Pathology, Faculty of Veterinary Medicine, University of Liège, B43 Sart-Tilman, B-4000 Liege, Belgium. sandra.jolly@ulg.ac.be
Desmecht
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D000818:Animals; D001980:Bronchi / Q000187:drug effects / Q000378:metabolism*; D002417:Cattle; D002927:Cimetidine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006632:Histamine / Q000494:pharmacology / Q000502:physiology*; D006635:Histamine H2 Antagonists / Q000494:pharmacology; D009126:Muscle Relaxation / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000378:metabolism*; D010880:Piperidines / Q000494:pharmacology; D011970:Receptors, Histamine H2 / Q000378:metabolism; D018100:Receptors, Histamine H3 / Q000378:metabolism; D020545:Respiratory Mucosa / Q000187:drug effects / Q000378:metabolism; D014132:Trachea / Q000187:drug effects / Q000378:metabolism*
D006635:Histamine H2 Antagonists; D010880:Piperidines; D011970:Receptors, Histamine H2; D018100:Receptors, Histamine H3; D002927:Cimetidine; D006632:Histamine; C052075:thioperamide