Cysteinyl Leukotrienes Induce Nasal Symptoms of Allergic Rhinitis via a Receptor-Mediated Mechanism in Guinea Pigs

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Author(s)

Abstract

To examine whether cysteinyl leukotrienes (cysLTs: LTC<SUB>4</SUB>, LTD<SUB>4</SUB> and LTE<SUB>4</SUB>) induce symptoms of allergic rhinitis via their receptors, we studied the following: i) the specific binding of radiolabeled cysLTs to guinea pig nasal mucosa membrane and ii) effects of nasal LTD<SUB>4</SUB> challenge in normal guinea pigs. The binding study indicated that there was a single population of binding sites for LTC<SUB>4</SUB>, LTD<SUB>4</SUB> and LTE<SUB>4</SUB> with Kd and B<SUB>max</SUB> values of 34.9±2.0, 0.252±0.015 and 0.589±0.039 nM and 10, 140±490, 122± 11 and 306±23 fmol/mg protein, respectively. The in vivo study showed that topical nasal challenge of LTD4 (0.1 30 μg/nose) increased nasal secretion, nasal airway resistance and nasal eosinophil infiltration without inducing sneezing. While the increases in nasal secretion and nasal airway resistance were transient, peaking 10 to 20 min after LTD<SUB>4</SUB> challenge, nasal eosinophil infiltration persisted at least until 24 hr post-challenge. These nasal symptoms were dose-dependently suppressed by oral administrations of pranlukast (0.3-3 mg/kg). The results suggest that cysLTs cause not only early-phase symptoms but also nasal eosinophil migration, a characteristic associated with the late-phase symptom of allergic rhinitis, via a receptormediated mechanism. Cysteinyl leukotrienes, thus, may be important mediators in allergic rhinitis.

Journal

  • The Japanese Journal of Pharmacology

    The Japanese Journal of Pharmacology 75(4), 355-362, 1997-12-01

    The Japanese Pharmacological Society

References:  21

Cited by:  9

Codes

  • NII Article ID (NAID)
    10008190427
  • NII NACSIS-CAT ID (NCID)
    AA00691188
  • Text Lang
    ENG
  • Article Type
    Journal Article
  • ISSN
    00215198
  • NDL Article ID
    4371101
  • NDL Source Classification
    ZS51(科学技術--薬学)
  • NDL Call No.
    Z53-D199
  • Data Source
    CJP  CJPref  NDL  J-STAGE 
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