Involvement of chemical mediators in nasal allergic responses of HDC-KO mice

Md Ashequr Rahman, Toshio Inoue, Takashi Ishikawa, Rie Yatsuzuka, Hiroshi Ohtsu, Chiaki Kamei

Research output: Contribution to journalArticlepeer-review

7 Citations (Scopus)

Abstract

The present study was undertaken to investigate the involvement of chemical mediators in nasal allergic responses using histidine decarboxylase knockout (HDC-KO) mice. An allergic rhinitis model was developed in HDC-KO and wild-type mice by the intraperitoneal injection of ovalbumin, aluminum hydroxide gel and pertussis toxin. Five days later, they were boosted by a subcutaneous injection of ovalbumin into the back. From day 18 after the first immunization to day 39, intranasal sensitization with ovalbumin was performed every day and the severity of allergic rhinitis was observed by measuring nasal allergic responses and total IgE levels. It was found that the intranasal administration of antigen caused a significant increase of nasal sneezing and rubbing from day 25 to day 39 both in sensitized HDC-KO and wild-type mice. In addition, a significant elevation of total IgE levels in serum was also found both in sensitized HDC-KO and wild-type mice from day 18 to day 39 after the first immunization. L-733,060, a tachykinin NK1 receptor antagonist at a dose of 10 mg/kg (s.c.), resulted in the dose-dependent inhibition of nasal allergic responses induced by antigen in both HDC-KO and wild-type mice. In addition, both chlorpheniramine at doses of 3 and 10 mg/kg (p.o.) and BW A868C at doses of 0.3 and 1 mg/kg (i.v.) also showed a dose-related reduction of the nasal allergic responses induced by antigen in sensitized wild-type mice. On the other hand, they had no effects on the nasal signs induced by antigen in HDC-KO mice. From these results, it was revealed that substance P induces nasal allergic responses in the mouse model of chronic allergic rhinitis through the activation of tachykinin NK1 receptors. Therefore, it can be concluded that not only histamine, but also substance P and prostaglandin D2, participated in the nasal allergic responses induced by antigen in mice.

Original languageEnglish
Pages (from-to)245-251
Number of pages7
JournalEuropean Journal of Pharmacology
Volume567
Issue number3
DOIs
Publication statusPublished - 2007 Jul 19

Keywords

  • BW A868C
  • C57BL/6
  • Chlorpheniramine
  • HDC (histidine decarboxylase) knockout mice
  • Histamine
  • L-733,060
  • Nasal allergic response
  • Nasal rubbing
  • Prostaglandin D
  • Sneezing

ASJC Scopus subject areas

  • Pharmacology

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