Arabinogalactan- and dextran-induced ear inflammation in mice: differential inhibition by H1-antihistamines, 5-HT-serotonin antagonists and lipoxygenase blockers.
Intravenous injection of arabinogalactan or dextran together with pontamine sky-blue dye into mice increased vascular permeability and led to marked blueing of the ears. Arabinogalactan caused a rapidly progressing ear blueing (maximal coloration 20-30 min after injection). This response was suppressed by pretreating the animals with the histamine H1-antihistamines levocabastine and loratadine. In contrast, dextran induced a slowly evolving ear inflammation (maximal coloration 60-90 min after injection), which was blocked by the 5-HT-serotonin antagonists cinanserin, metergoline and ritanserin. Furthermore, the dextran reaction was inhibited by the lipoxygenase (LO)/cyclooxygenase (CO) inhibitors BW540C, BW755C and phenidone and by the specific 5-LO inhibitor AA-861. Both arabinogalactan and dextran responses were inhibited by aprotinin, a kallikrein inhibitor, and the mixed H1/5-HT antagonists astemizole and azatadine. The inflammogenic activity of the polysaccharides was not affected by administration of the CO inhibitors indomethacin and suprofen, the thromboxane synthetase inhibitor dazoxiben, the H2-antihistamines cimetidine and ranitidine, the anticholinergics isopropamide or the PAF-antagonist L-652, 731. These data indicate the existence of distinctive endogenous molecules that mediate the pinnal extravasation reaction to both polysaccharides: histamine for arabinogalactan, serotonin and lipoxygenase-derived arachidonic acid metabolites for dextran.
van Wauwe
J P
JP
Janssen Research Foundation, Beerse, Belgium.
Goossens
J G
JG
D015772:4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-amine; D000818:Animals; D007611:Aprotinin / Q000627:therapeutic use; D016589:Astemizole; D001562:Benzimidazoles / Q000627:therapeutic use; D016227:Benzoquinones; D002928:Cinanserin / Q000627:therapeutic use; D003533:Cyproheptadine / Q000031:analogs & derivatives / Q000627:therapeutic use; D003911:Dextrans; D005685:Galactans; D006634:Histamine H1 Antagonists / Q000627:therapeutic use*; D007700:Kinetics; D016859:Lipoxygenase Inhibitors; D008297:Male; D008711:Metergoline / Q000627:therapeutic use; D051379:Mice; D010031:Otitis / Q000139:chemically induced / Q000517:prevention & control*; D010880:Piperidines / Q000627:therapeutic use; D011720:Pyrazoles / Q000627:therapeutic use; D011809:Quinones / Q000494:pharmacology; D016713:Ritanserin; D012702:Serotonin Antagonists / Q000627:therapeutic use*
D001562:Benzimidazoles; D016227:Benzoquinones; D003911:Dextrans; D005685:Galactans; D006634:Histamine H1 Antagonists; D016859:Lipoxygenase Inhibitors; D010880:Piperidines; D011720:Pyrazoles; D011809:Quinones; D012702:Serotonin Antagonists; D016713:Ritanserin; D008711:Metergoline; D003533:Cyproheptadine; D015772:4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-amine; D016589:Astemizole; C036837:2,3,5-trimethyl-6-(12-hydroxy-5,10-dodecadiynyl)-1,4-benzoquinone; C046216:BW 540C; D007611:Aprotinin; C006656:azatadine; C015429:phenidone; D002928:Cinanserin; C005653:arabinogalactan