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OtherPROSTAGLANDINS, LEUKOTRIENES AND OTHER EICOSANOIDS

Involvement of Thromboxane A2 and Histamine in Experimental Allergic Rhinitis of Guinea Pigs

M. Yamasaki, T. Matsumoto, S. Fukuda, T. Nakayama, H. Nagaya and Y. Ashida
Journal of Pharmacology and Experimental Therapeutics March 1997, 280 (3) 1471-1479;
M. Yamasaki
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T. Matsumoto
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S. Fukuda
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T. Nakayama
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H. Nagaya
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Y. Ashida
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Abstract

To identify the chemical mediators involved in the pathogenesis of allergic rhinitis, we studied the effects of the thromboxane (TX) A2 receptor antagonist seratrodast, the peptide leukotriene receptor antagonist pranlukast and the antihistamine azelastine using a guinea pig model of allergic rhinitis. In guinea pigs actively sensitized by aerosol inhalation of antigen, antigen challenge into the nasal cavity increased both the nasal vascular permeability and the intranasal pressure; it also induced swelling of the nasal mucosa, which was evaluated by magnetic resonance imaging. Both seratrodast and azelastine significantly inhibited these antigen-induced responses when the drugs were administered p.o. 1 hr before antigen challenge. Also, the TX synthetase inhibitor ozagrel reduced the antigen-induced increase in nasal vascular permeability. On the other hand, pranlukast had little effect on the antigen-induced increases in nasal vascular permeability and intranasal pressure. Perfusions and inhalations of U-46619, a stable TXA2 mimetic, or of histamine into the nasal cavity caused concentration-dependent increases in nasal vascular permeability and intranasal pressure in normal guinea pigs. Leukotriene C4 also induced these responses, but the maximal responses to leukotriene C4 were less than the maximal responses to U-46619 or histamine. On the other hand, these responses were not induced by prostaglandin D2 or prostaglandin F2α. Moreover, the U-46619- and histamine-induced increases in vascular permeability and intranasal pressure were significantly inhibited by seratrodast and azelastine, respectively. In addition, levels of TXB2, a stable breakdown product of TXA2, and histamine in nasal lavage fluid increased after antigen challenge in actively sensitized guinea pigs. These results suggest that TXA2 and histamine play important roles in the pathogenesis of experimental allergic rhinitis in guinea pigs.

Footnotes

  • Send reprint requests to: Masashi Yamasaki, Pharmaceutical Research Laboratories I, Pharmaceutical Research Division, Takeda Chemical Industries, Ltd., 2-17-85 Jusohonmachi, Yodogawa-ku, Osaka 532, Japan.

  • Abbreviations:
    AUC
    area under the response curve
    EDTA
    ethylenediaminetetraacetic acid disodium salt
    LTC4
    leukotriene C4
    MRI
    magnetic resonance imaging
    OA
    ovalbumin
    PG
    prostaglandin
    TX
    thromboxane
    • Received April 15, 1996.
    • Accepted November 11, 1996.
  • The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics
Vol. 280, Issue 3
1 Mar 1997
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OtherPROSTAGLANDINS, LEUKOTRIENES AND OTHER EICOSANOIDS

Involvement of Thromboxane A2 and Histamine in Experimental Allergic Rhinitis of Guinea Pigs

M. Yamasaki, T. Matsumoto, S. Fukuda, T. Nakayama, H. Nagaya and Y. Ashida
Journal of Pharmacology and Experimental Therapeutics March 1, 1997, 280 (3) 1471-1479;

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OtherPROSTAGLANDINS, LEUKOTRIENES AND OTHER EICOSANOIDS

Involvement of Thromboxane A2 and Histamine in Experimental Allergic Rhinitis of Guinea Pigs

M. Yamasaki, T. Matsumoto, S. Fukuda, T. Nakayama, H. Nagaya and Y. Ashida
Journal of Pharmacology and Experimental Therapeutics March 1, 1997, 280 (3) 1471-1479;
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