2005 Fiscal Year Final Research Report Summary
Analyses of induction mechanisms underlying nasal blockage and nasal hyperresponsiveness using an experimental model of allergic rhinitis
| Project/Area Number |
15590080
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Biological pharmacy
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| Research Institution | Kyoto Pharmaceutical University |
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Principal Investigator |
KOHNO Shigekatsu Kyoto Pharmaceutical University, Faculty of Pharmacy, Professor, 薬学部, 教授 (50082988)
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| Co-Investigator(Kenkyū-buntansha) |
NABE Takeshi Kyoto Pharmaceutical University, Faculty of Pharmacy, Associate Professor, 薬学部, 助教授 (40228078)
YASUI Hiroyuki Kyoto Pharmaceutical University, Faculty of Pharmacy, Associate Professor, 薬学部, 助教授 (20278443)
TAKENAKA Hiroshi Osaka Medical College, Faculty of Medicine, Professor, 医学部, 教授 (40137162)
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| Project Period (FY) |
2003 – 2005
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| Keywords | Allergic rhinitis / Pollenosis / Nasal blockage / Nasal hyperresponsiveness / Arachidonic acid metabolites / Kinins / Immunotherapy / Anti-allergic drugs |
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| Research Abstract |
We have developed an experimental allergic rhinitis model by repetitive inhalation challenges with Japanese cedar pollen in sensitized guinea pigs. In this model, sneezing is induced immediately after challenges, and biphasic nasal blockage were also induced with peaks at 1-2 and 4-6 h after challenges. Furthermore, nasal hyperresponsiveness to non-specific stimuli was developed 10 h-2 days after challenges. Among these symptoms, nasal blockage and nasal hyperresponsiveness are serious symptoms for patient's daily life. Medicines to relieve these signs are only corticosteroids, which shows various side effects.
In this study, in order to analyze induction mechanisms underlying nasal blockage and nasal hyperresponsiveness, roles of several mediators are evaluated. In addition, we assessed effect of oral immunotherapy on inductions of these symptoms as a fundamental therapeutic strategy. Results obtained are as follows :
1.It was strongly suggested that the nasal hyperresponsiveness is ind
… More
uced by kinins such as bradykinin that are produced immediately after antigen challenge through activation of B_1 and B_2 receptors, which have been newly and constitutively expressed on the nasal mucosa.
2.Arachidonic acid metabolites, cysteinyl leukotrienes and thromboxane A_2 are involved in the induction of the antigen-induced late phase nasal blockage through synergistically acting on the nasal mucosa.
3.When the pollen extract was orally administered during the challenging period, inductions of nasal blockage and nasal hyperresponsiveness were strongly suppressed.
In conclusion, arachidonic acid metabolites described above and kinins are suggested to play important roles in inductions of nasal blockage and nasal hyperresponsiveness, respectively. Especially, because antagonists against kinin receptors have not been clinically used, this class of compounds could be new therapeutic drugs for allergic rhinitis. In addition, we hope that our present result showing the effectiveness of the oral immunotherapy could stimulate further clinical examinations evaluating effects of the immunotherapy on allergic rhinitis symptoms. Less
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