Journal
BRITISH JOURNAL OF PHARMACOLOGY
Volume 144, Issue 6, Pages 867-874Publisher
WILEY
DOI: 10.1038/sj.bjp.0706118
Keywords
histamine; nasal airway; human; H-3 receptor; sympathetic nerves
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1 The aim of this study was to investigate the mechanisms by which histamine causes nasal blockage. Histamine, 40-800 mu g, intranasally into each nostril, induced significant blockage of the nasal airway in normal human subjects, as measured by acoustic rhinometry. 2 Oral pretreatment with cetirizine, 5-30 mg, the H-1 antagonist, failed to reverse completely the nasal blockage induced by histamine, 400 mg. 3 Dimaprit, 50-200 mu g, the H-2 agonist, intranasally, caused nasal blockage, which was reversed by oral pretreatment with ranitidine, 75 mg, the H-2 antagonist. 4 A combination of cetirizine, 20 mg, and ranitidine, 75 mg, caused greater inhibition of the nasal blockage caused by histamine, 400 mu g, than cetirizine alone. In the presence of both antagonists, there was residual histamine-induced nasal blockage. 5 R-alpha-methylhistamine (R-alpha-MeH), 100-600 mu g, the H-3 agonist, intranasally, caused nasal blockage, which was not inhibited by either cetirizine or ranitidine. 6 Thioperamide, 700 mu g, the H-3 antagonist, intranasally, reversed the R-alpha-MeH-induced nasal blockage. Thioperamide alone had no significant action on the nasal blockage induced by histamine, 400 and 1000 mu g, but, in the presence of cetirizine, 20 mg, thioperamide further reduced the histamine-induced nasal blockage. 7 Corynanthine, 2 mg, the alpha(1)-adrenoceptor antagonist, administered intranasally, caused nasal blockage. 8 Corynanthine produced a greater increase in nasal blockage when in combination with bradykinin compared to its combination with R-alpha-MeH. 9 There appears to be a contribution of H-1, H-2 and H-3 receptors to histamine-induced nasal blockage in normal human subjects. The sympathetic nervous system actively maintains nasal patency and we suggest that activation of nasal H-3 receptors may downregulate sympathetic activity.
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