Prostaglandin D2 Modulates Neuronal Excitation of the Trigeminal Ganglion to Augment Allergic Rhinitis in Guinea Pigs

Prostaglandin D 2 (PGD 2 ) is involved in the pathogenesis of allergic rhinitis. However, the sensory nervous system–mediated contributions of PGD 2 to the symptoms of allergic rhinitis remain unclear. We investigated the involvement of PGD 2 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 PGD 2 , histamine, or a combination of PGD 2 and histamine. In situ hybridization for PGD 2 receptor 1 (DP 1 ) mRNA transcripts and immunohistochemical analysis of histamine H 1 receptor protein expression in guinea pig trigeminal ganglion (TRG) were performed. The effects of DP 1 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 PGD 2 . PGD 2 augmented histamine-induced responses, whereas pretreatment with a DP 1 receptor–selective antagonist completely suppressed PGD 2 -induced augmentation. DP 1 receptor mRNA transcripts and H 1 receptor protein expression could be detected in TRG neurons. Moreover, a DP 1 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 PGD 2 –DP 1 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 DP 1 receptor antagonist has therapeutic potential for the treatment of allergic rhinitis.