Prostaglandin D2 (PGD2) is involved in the pathogenesis of allergic rhinitis. However, the sensory nervous system–mediated contributions of PGD2 to the symptoms of allergic rhinitis remain unclear. We investigated the involvement of PGD2 in 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 PGD2 and histamine. In situ hybridization for PGD2 receptor 1 (DP1) mRNA transcripts and immunohistochemical analysis of histamine H1 receptor protein expression in guinea pig trigeminal ganglion (TRG) were performed. The effects of DP1 receptor 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. PGD2 augmented histamine-induced responses, whereas pretreatment with a DP1 receptor–selective antagonist completely suppressed PGD2-induced augmentation. DP1 receptor mRNA transcripts and H1 receptor protein expression could be detected in TRG neurons. Moreover, a DP1 receptor 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–DP1 receptor 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 DP1 receptor antagonist has therapeutic potential for the treatment of allergic rhinitis.
- Received December 3, 2015.
- Accepted March 2, 2016.
Y.N. and K.G. contributed equally to this work.
- Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics