Tags

Type your tag names separated by a space and hit enter

Important roles of tachykinins in the development of allergic nasal hyperresponsiveness in guinea-pigs.
Clin Exp Allergy. 2009 Jan; 39(1):138-46.CE

Abstract

BACKGROUND

Although it has been suggested that the use of tachykinin receptor antagonists might prove to be an effective treatment for allergic rhinitis (AR), they are not used clinically. Therefore, we decided to examine the effects of tachykinin receptor antagonists on AR symptoms in an appropriate experimental model.

OBJECTIVE

To evaluate newly developed tachykinin receptor antagonists in a Japanese cedar pollen-induced AR model and to determine their effect on allergen-induced sneezing, nasal blockage, and nasal hyperresponsiveness (NHR).

METHODS

Sensitized guinea-pigs were challenged by forced inhalation of pollen once every week. Sneezing and nasal blockage were observed after pollen challenges. NHR (nasal blockage) to an intranasal application of leukotriene D(4) was assessed 2 days after an antigen challenge. We also evaluated whether intranasal dosing with a tachykinin causes NHR. NK(1) and NK(2) receptor antagonists were administered before an intranasal treatment with antigen or tachykinin. Amounts of tachykinins present in nasal cavity lavage fluid were measured by an enzyme immunoassay.

RESULTS

Although an NK(1) and NK(2) receptor dual antagonist showed no effect on pollen-induced sneezing and biphasic nasal blockage, it did completely suppress the development of NHR. Experiments using specific NK(1) or NK(2) receptor antagonists revealed that NK(2) receptor activation was preferentially involved in the development of hyperresponsiveness. Increases in the levels of substance P (SP) and neurokinin A (NKA) in the nasal tissue were noted 20 min-1 h after the challenge. Intranasal instillation of either SP or NKA-induced NHR, which was almost completely inhibited by NK(2) receptor antagonists and partially inhibited by NK(1) receptor antagonists.

CONCLUSIONS

SP and NKA, which are released early after the challenge, mediate the development of NHR by preferentially activating NK(2) receptors. Therefore, NK(2) receptor antagonists might prove to be effective treatment of AR.

Authors+Show Affiliations

Department of Pharmacology, Kyoto Pharmaceutical University, Kyoto, Japan. nabe@mb.kyoto-phu.ac.jpNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18778270

Citation

Nabe, T, et al. "Important Roles of Tachykinins in the Development of Allergic Nasal Hyperresponsiveness in Guinea-pigs." Clinical and Experimental Allergy : Journal of the British Society for Allergy and Clinical Immunology, vol. 39, no. 1, 2009, pp. 138-46.
Nabe T, Tsuzuike N, Ohtani Y, et al. Important roles of tachykinins in the development of allergic nasal hyperresponsiveness in guinea-pigs. Clin Exp Allergy. 2009;39(1):138-46.
Nabe, T., Tsuzuike, N., Ohtani, Y., Mizutani, N., Watanabe, S., Fujii, M., Yoshimura, M., Nagasawa, M., & Kohno, S. (2009). Important roles of tachykinins in the development of allergic nasal hyperresponsiveness in guinea-pigs. Clinical and Experimental Allergy : Journal of the British Society for Allergy and Clinical Immunology, 39(1), 138-46. https://doi.org/10.1111/j.1365-2222.2008.03097.x
Nabe T, et al. Important Roles of Tachykinins in the Development of Allergic Nasal Hyperresponsiveness in Guinea-pigs. Clin Exp Allergy. 2009;39(1):138-46. PubMed PMID: 18778270.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Important roles of tachykinins in the development of allergic nasal hyperresponsiveness in guinea-pigs. AU - Nabe,T, AU - Tsuzuike,N, AU - Ohtani,Y, AU - Mizutani,N, AU - Watanabe,S, AU - Fujii,M, AU - Yoshimura,M, AU - Nagasawa,M, AU - Kohno,S, Y1 - 2008/09/04/ PY - 2008/9/10/pubmed PY - 2009/2/14/medline PY - 2008/9/10/entrez SP - 138 EP - 46 JF - Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology JO - Clin. Exp. Allergy VL - 39 IS - 1 N2 - BACKGROUND: Although it has been suggested that the use of tachykinin receptor antagonists might prove to be an effective treatment for allergic rhinitis (AR), they are not used clinically. Therefore, we decided to examine the effects of tachykinin receptor antagonists on AR symptoms in an appropriate experimental model. OBJECTIVE: To evaluate newly developed tachykinin receptor antagonists in a Japanese cedar pollen-induced AR model and to determine their effect on allergen-induced sneezing, nasal blockage, and nasal hyperresponsiveness (NHR). METHODS: Sensitized guinea-pigs were challenged by forced inhalation of pollen once every week. Sneezing and nasal blockage were observed after pollen challenges. NHR (nasal blockage) to an intranasal application of leukotriene D(4) was assessed 2 days after an antigen challenge. We also evaluated whether intranasal dosing with a tachykinin causes NHR. NK(1) and NK(2) receptor antagonists were administered before an intranasal treatment with antigen or tachykinin. Amounts of tachykinins present in nasal cavity lavage fluid were measured by an enzyme immunoassay. RESULTS: Although an NK(1) and NK(2) receptor dual antagonist showed no effect on pollen-induced sneezing and biphasic nasal blockage, it did completely suppress the development of NHR. Experiments using specific NK(1) or NK(2) receptor antagonists revealed that NK(2) receptor activation was preferentially involved in the development of hyperresponsiveness. Increases in the levels of substance P (SP) and neurokinin A (NKA) in the nasal tissue were noted 20 min-1 h after the challenge. Intranasal instillation of either SP or NKA-induced NHR, which was almost completely inhibited by NK(2) receptor antagonists and partially inhibited by NK(1) receptor antagonists. CONCLUSIONS: SP and NKA, which are released early after the challenge, mediate the development of NHR by preferentially activating NK(2) receptors. Therefore, NK(2) receptor antagonists might prove to be effective treatment of AR. SN - 1365-2222 UR - https://www.unboundmedicine.com/medline/citation/18778270/Important_roles_of_tachykinins_in_the_development_of_allergic_nasal_hyperresponsiveness_in_guinea_pigs_ L2 - https://doi.org/10.1111/j.1365-2222.2008.03097.x DB - PRIME DP - Unbound Medicine ER -