The Phosphodiesterase 4 Inhibitor Prevents Antigen-induced Biphasic Nasal Obstruction in Brown Norway Rats
Background: Nasal obstruction is considered the most serious problem for patients with allergic rhinitis. We have previously established a model of nasal obstruction in guinea pigs. In the present study, we tried to establish an allergic model of nasal obstruction using Brown Norway (BN) rats to eva...
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| Format: | Article |
| Language: | English |
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Elsevier
2005-01-01
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| Series: | Allergology International |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1323893015310558 |
| _version_ | 1818505271910072320 |
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| author | Hirokazu Kawasaki Toshihiko Kaise Haruhiko Manabe Akihiko Watanabe |
| author_facet | Hirokazu Kawasaki Toshihiko Kaise Haruhiko Manabe Akihiko Watanabe |
| author_sort | Hirokazu Kawasaki |
| collection | DOAJ |
| description | Background: Nasal obstruction is considered the most serious problem for patients with allergic rhinitis. We have previously established a model of nasal obstruction in guinea pigs. In the present study, we tried to establish an allergic model of nasal obstruction using Brown Norway (BN) rats to evaluate the effects of phosphodiesterase (PDE) 4 inhibitors in this model.
Methods: The volume of the nasal cavity was measured with an acoustic rhinometer. Decrease in the volume of the nasal cavity was taken as nasal obstruction. BN rats were actively sensitized with ovalbumin conjugated with aluminium hydroxide. Intranasal antigen instillation induced biphasic nasal obstruction in sensitized BN rats.
Results: Early and late phase responses (EPR and LPR) were observed peaking at 0.5 and 6 hours after the antigen challenge, respectively. Chlorpheniramine did not inhibit EPR or LPR at 10 mg/kg, although the dose was sufficient for the compound to exert its anti-histamine activity. Prednisolone inhibited both responses at 30 mg/kg. Rolipram and CDP-840, PDE4 inhibitors, inhibited both responses at 100 mg/kg. KF19514, a PDE1/4 dual inhibitor, inhibited EPR at 0.1 mg/kg or more and inhibited LPR at 10 mg/kg.
Conclusions: The present study provides a simple model of allergic biphasic nasal obstruction in BN rats, and also suggests that the PDE4 inhibitor may alleviate nasal obstruction in patients with allergic rhinitis. |
| first_indexed | 2024-12-10T21:48:26Z |
| format | Article |
| id | doaj.art-60bcdb38c8a4460191608633e2d29b81 |
| institution | Directory Open Access Journal |
| issn | 1323-8930 |
| language | English |
| last_indexed | 2024-12-10T21:48:26Z |
| publishDate | 2005-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Allergology International |
| spelling | doaj.art-60bcdb38c8a4460191608633e2d29b812022-12-22T01:32:18ZengElsevierAllergology International1323-89302005-01-0154342743310.2332/allergolint.54.427The Phosphodiesterase 4 Inhibitor Prevents Antigen-induced Biphasic Nasal Obstruction in Brown Norway RatsHirokazu Kawasaki0Toshihiko Kaise1Haruhiko Manabe2Akihiko Watanabe3Department of Allergy Research, Pharmaceutical Research Center, Kyowa Hakko Kogyo Co., Ltd., Shizuoka, Japan.Department of Allergy Research, Pharmaceutical Research Center, Kyowa Hakko Kogyo Co., Ltd., Shizuoka, Japan.Department of Allergy Research, Pharmaceutical Research Center, Kyowa Hakko Kogyo Co., Ltd., Shizuoka, Japan.Department of Allergy Research, Pharmaceutical Research Center, Kyowa Hakko Kogyo Co., Ltd., Shizuoka, Japan.Background: Nasal obstruction is considered the most serious problem for patients with allergic rhinitis. We have previously established a model of nasal obstruction in guinea pigs. In the present study, we tried to establish an allergic model of nasal obstruction using Brown Norway (BN) rats to evaluate the effects of phosphodiesterase (PDE) 4 inhibitors in this model. Methods: The volume of the nasal cavity was measured with an acoustic rhinometer. Decrease in the volume of the nasal cavity was taken as nasal obstruction. BN rats were actively sensitized with ovalbumin conjugated with aluminium hydroxide. Intranasal antigen instillation induced biphasic nasal obstruction in sensitized BN rats. Results: Early and late phase responses (EPR and LPR) were observed peaking at 0.5 and 6 hours after the antigen challenge, respectively. Chlorpheniramine did not inhibit EPR or LPR at 10 mg/kg, although the dose was sufficient for the compound to exert its anti-histamine activity. Prednisolone inhibited both responses at 30 mg/kg. Rolipram and CDP-840, PDE4 inhibitors, inhibited both responses at 100 mg/kg. KF19514, a PDE1/4 dual inhibitor, inhibited EPR at 0.1 mg/kg or more and inhibited LPR at 10 mg/kg. Conclusions: The present study provides a simple model of allergic biphasic nasal obstruction in BN rats, and also suggests that the PDE4 inhibitor may alleviate nasal obstruction in patients with allergic rhinitis.http://www.sciencedirect.com/science/article/pii/S1323893015310558acoustic rhinometryallergic rhinitisBN ratnasal obstructionPDE inhibitor |
| spellingShingle | Hirokazu Kawasaki Toshihiko Kaise Haruhiko Manabe Akihiko Watanabe The Phosphodiesterase 4 Inhibitor Prevents Antigen-induced Biphasic Nasal Obstruction in Brown Norway Rats Allergology International acoustic rhinometry allergic rhinitis BN rat nasal obstruction PDE inhibitor |
| title | The Phosphodiesterase 4 Inhibitor Prevents Antigen-induced Biphasic Nasal Obstruction in Brown Norway Rats |
| title_full | The Phosphodiesterase 4 Inhibitor Prevents Antigen-induced Biphasic Nasal Obstruction in Brown Norway Rats |
| title_fullStr | The Phosphodiesterase 4 Inhibitor Prevents Antigen-induced Biphasic Nasal Obstruction in Brown Norway Rats |
| title_full_unstemmed | The Phosphodiesterase 4 Inhibitor Prevents Antigen-induced Biphasic Nasal Obstruction in Brown Norway Rats |
| title_short | The Phosphodiesterase 4 Inhibitor Prevents Antigen-induced Biphasic Nasal Obstruction in Brown Norway Rats |
| title_sort | phosphodiesterase 4 inhibitor prevents antigen induced biphasic nasal obstruction in brown norway rats |
| topic | acoustic rhinometry allergic rhinitis BN rat nasal obstruction PDE inhibitor |
| url | http://www.sciencedirect.com/science/article/pii/S1323893015310558 |
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