Manabu Fujita, Naoki Nakagawa, Yasuo Yonetomi, Hiroshi Takeda, Kazuhito
Kawabata (*) and Hiroyuki Ohno
Minase Research Institute, Ono Pharmaceutical Co., Ltd., 3-1-1 Sakurai,
Shimamoto-cho, Mishima-gun, Osaka 618, Japan
(*) To whom correspondence should be addressed.
Abstract: To examine whether cysteinyl leukotrienes (cysLTs:
LTC4, LTD4 and LTE4) 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 LTD4 challenge
in normal guinea pigs. The binding study indicated that there was a single
population of binding sites for LTC4, LTD4 and LTE4 with Kd and Bmax 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 microg/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 LTD4 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 receptor-mediated
mechanism. Cysteinyl leukotrienes, thus, may be important mediators in allergic
rhinitis.
Keywords: Cysteinyl leukotriene, Rhinitis, Eosinophil, Receptor, Pranlukast