Prostaglandin D2(
PGD2) is involved in the pathogenesis of
allergic rhinitis. However, the sensory nervous system-mediated contributions of PGD2to the symptoms of
allergic rhinitis remain unclear. We investigated the involvement of PGD2in these symptoms and in neuronal excitation by in vivo and ex vivo experiments. In an
ovalbumin-induced model of
allergic rhinitis in guinea pigs, the number of
sneezing, nasal rubbing, and nasal secretion events were assessed after the nasal cavity instillation of
PGD2,
histamine, or a combination of PGD2and
histamine. In situ hybridization for PGD2receptor 1 (DP1)
mRNA transcripts and immunohistochemical analysis of
histamine H1receptor
protein expression in guinea pig trigeminal ganglion (TRG) were performed. The effects of DP1receptor activation on the excitability of TRG neurons to electrical and
histamine stimuli were assessed using whole-cell patch-clamp recordings.
Histamine induced more
sneezing, nasal rubbing, and nasal secretion events than
PGD2 PGD2augmented
histamine-induced responses, whereas pretreatment with a DP1receptor-selective antagonist completely suppressed PGD2-induced augmentation. DP1receptor
mRNA transcripts and H1receptor
protein expression could be detected in TRG neurons. Moreover, a DP1receptor agonist caused significant increases in the number of
histamine-induced action potentials and depolarization, and reduced the current threshold in small-diameter neurons. Our findings show that PGD2-DP1receptor signaling augments the symptoms of
allergic rhinitis via the sensory nervous system by modulating nasal neuronal activation to various stimuli, such as
histamine. These findings suggest that DP1receptor antagonist has therapeutic potential for the treatment of
allergic rhinitis.