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Involvement of thromboxane A2 and peptide leukotrienes in early and late phase nasal blockage in a guinea pig model of allergic rhinitis.
Inflamm Res. 2001 Sep; 50(9):466-73.IR

Abstract

OBJECTIVE AND DESIGN

We investigated the effects of the thromboxane (TX) A2 antagonist seratrodast, the peptide leukotriene (p-LT) antagonist pranlukast, the antihistaminic drug terfenadine and the glucocorticoid dexamethasone on antigen-induced sneezing, biphasic nasal blockage and nasal hyperresponsiveness to histamine using a guinea pig model of allergic rhinitis.

SUBJECTS

Male Hartley guinea pigs were used.

TREATMENT

Intranasally sensitized guinea pigs were challenged once every week for 13 weeks by inhalation of Japanese cedar pollen as the antigen. Dexamethasone and other agents were administered orally 3 and 1 h, respectively, before the 4th, 6th and 13th challenge.

METHODS

Sneezing frequency and the change in specific airway resistance (sRaw) were measured at these challenges. Two days after the 13th challenge, nasal responsiveness to histamine was evaluated by measuring sRaw after intranasal instillation of increasing doses of histamine. Moreover, the levels of TXB2, p-LTs and histamine were estimated in nasal cavity lavage fluid (NCLF) collected at the 13th challenge.

RESULTS

Only terfenadine (10 mg/kg) significantly inhibited sneezing at any challenge time. Seratrodast (3 and 10 mg/ kg), pranlukast (30 mg/kg) and dexamethasone (10 mg/kg), but not terfenadine, suppressed both the early and late phase elevation of sRaw (biphasic nasal blockage), although the degree of inhibition on the early phase response varied with the challenge time. In contrast, the development of nasal hyperresponsiveness to histamine was inhibited by only dexamethasone. Furthermore, biphasic increases in TXB2, p-LTs and histamine in NCLF were observed after the challenge in sensitized animals.

CONCLUSIONS

These results suggest that TXA2 and p-LTs, but not histamine, play important roles in both the early and the late phase nasal blockage in this model of allergic rhinitis.

Authors+Show Affiliations

Pharmaceutical Research Division, Takeda Chemical Industries, Ltd, Osaka, Japan. Yamasaki_Masashi@takeda.co.jpNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

11603852

Citation

Yamasaki, M, et al. "Involvement of Thromboxane A2 and Peptide Leukotrienes in Early and Late Phase Nasal Blockage in a Guinea Pig Model of Allergic Rhinitis." Inflammation Research : Official Journal of the European Histamine Research Society ... [et Al.], vol. 50, no. 9, 2001, pp. 466-73.
Yamasaki M, Mizutani N, Sasaki K, et al. Involvement of thromboxane A2 and peptide leukotrienes in early and late phase nasal blockage in a guinea pig model of allergic rhinitis. Inflamm Res. 2001;50(9):466-73.
Yamasaki, M., Mizutani, N., Sasaki, K., Nabe, T., Matsumoto, T., Ashida, Y., & Kohno, S. (2001). Involvement of thromboxane A2 and peptide leukotrienes in early and late phase nasal blockage in a guinea pig model of allergic rhinitis. Inflammation Research : Official Journal of the European Histamine Research Society ... [et Al.], 50(9), 466-73.
Yamasaki M, et al. Involvement of Thromboxane A2 and Peptide Leukotrienes in Early and Late Phase Nasal Blockage in a Guinea Pig Model of Allergic Rhinitis. Inflamm Res. 2001;50(9):466-73. PubMed PMID: 11603852.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Involvement of thromboxane A2 and peptide leukotrienes in early and late phase nasal blockage in a guinea pig model of allergic rhinitis. AU - Yamasaki,M, AU - Mizutani,N, AU - Sasaki,K, AU - Nabe,T, AU - Matsumoto,T, AU - Ashida,Y, AU - Kohno,S, PY - 2001/10/18/pubmed PY - 2002/3/22/medline PY - 2001/10/18/entrez SP - 466 EP - 73 JF - Inflammation research : official journal of the European Histamine Research Society ... [et al.] JO - Inflamm. Res. VL - 50 IS - 9 N2 - OBJECTIVE AND DESIGN: We investigated the effects of the thromboxane (TX) A2 antagonist seratrodast, the peptide leukotriene (p-LT) antagonist pranlukast, the antihistaminic drug terfenadine and the glucocorticoid dexamethasone on antigen-induced sneezing, biphasic nasal blockage and nasal hyperresponsiveness to histamine using a guinea pig model of allergic rhinitis. SUBJECTS: Male Hartley guinea pigs were used. TREATMENT: Intranasally sensitized guinea pigs were challenged once every week for 13 weeks by inhalation of Japanese cedar pollen as the antigen. Dexamethasone and other agents were administered orally 3 and 1 h, respectively, before the 4th, 6th and 13th challenge. METHODS: Sneezing frequency and the change in specific airway resistance (sRaw) were measured at these challenges. Two days after the 13th challenge, nasal responsiveness to histamine was evaluated by measuring sRaw after intranasal instillation of increasing doses of histamine. Moreover, the levels of TXB2, p-LTs and histamine were estimated in nasal cavity lavage fluid (NCLF) collected at the 13th challenge. RESULTS: Only terfenadine (10 mg/kg) significantly inhibited sneezing at any challenge time. Seratrodast (3 and 10 mg/ kg), pranlukast (30 mg/kg) and dexamethasone (10 mg/kg), but not terfenadine, suppressed both the early and late phase elevation of sRaw (biphasic nasal blockage), although the degree of inhibition on the early phase response varied with the challenge time. In contrast, the development of nasal hyperresponsiveness to histamine was inhibited by only dexamethasone. Furthermore, biphasic increases in TXB2, p-LTs and histamine in NCLF were observed after the challenge in sensitized animals. CONCLUSIONS: These results suggest that TXA2 and p-LTs, but not histamine, play important roles in both the early and the late phase nasal blockage in this model of allergic rhinitis. SN - 1023-3830 UR - https://www.unboundmedicine.com/medline/citation/11603852/Involvement_of_thromboxane_A2_and_peptide_leukotrienes_in_early_and_late_phase_nasal_blockage_in_a_guinea_pig_model_of_allergic_rhinitis_ L2 - https://dx.doi.org/10.1007/PL00000272 DB - PRIME DP - Unbound Medicine ER -