Effect of the potent and selective DP1 receptor antagonist, asapiprant (S-555739), in animal models of allergic rhinitis and allergic asthma

Go Takahashi, Fujio Asanuma, Noriko Suzuki, Maki Hattori, Shingo Sakamoto, Akira Kugimiya, Yasuhiko Tomita, Goro Kuwajima, William M. Abraham, Masashi Deguchi, Akinori Arimura, Michitaka Shichijo

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Prostaglandin (PG) D<inf>2</inf> elicits responses through either the DP<inf>1</inf> and/or DP<inf>2</inf> receptor. Experimental evidence suggests that stimulation of the DP<inf>1</inf> receptor contributes to allergic responses, such that antagonists are considered to be directed therapies for allergic diseases. In this study, we demonstrate the activity of a novel synthetic DP<inf>1</inf> receptor antagonist termed asapiprant (S-555739) for the DP<inf>1</inf> receptor and other receptors in vitro, and assess the efficacy of asapiprant in several animal models of allergic diseases. We determined the affinity and selectivity of asapiprant for the DP<inf>1</inf> receptor in binding assays. In the animal models of allergic rhinitis, changes in nasal resistance, nasal secretion, and cell infiltration in nasal mucosa were assessed after antigen challenge with and without asapiprant. Similarly, in the animal models of asthma, the effect of antigen challenge with and without asapiprant on antigen-induced bronchoconstriction, airway hyper-responsiveness, mucin production, and cell infiltration in lung were assessed. In binding studies, asapiprant exhibited high affinity and selectivity for the DP<inf>1</inf> receptor. Significant suppression of antigen-induced nasal resistance, nasal secretion, and cell infiltration in nasal mucosa was observed with asapiprant treatment. In addition, treatment with asapiprant suppressed antigen-induced asthmatic responses, airway hyper-responsiveness, and cell infiltration and mucin production in lung. These results show that asapiprant is a potent and selective DP<inf>1</inf> receptor antagonist, and exerts suppressive effects in the animal models of allergic diseases. Thus, asapiprant has potential as a novel therapy for allergic airway diseases.

Original languageEnglish (US)
Article number70151
Pages (from-to)15-23
Number of pages9
JournalEuropean Journal of Pharmacology
Volume765
DOIs
StatePublished - Aug 12 2015
Externally publishedYes

Fingerprint

Nose
Asthma
Animal Models
Respiratory Hypersensitivity
Antigens
Animal Disease Models
Nasal Mucosa
Mucins
Artificial Receptors
Prostaglandin D2
Lung
Bronchoconstriction
Allergic Rhinitis
Therapeutics

Keywords

  • Allergic rhinitis
  • Asapiprant
  • Nasal congestion
  • Prostaglandin D<inf>2</inf>
  • Synthetic DP<inf>1</inf> receptorantagonist

ASJC Scopus subject areas

  • Pharmacology

Cite this

Effect of the potent and selective DP1 receptor antagonist, asapiprant (S-555739), in animal models of allergic rhinitis and allergic asthma. / Takahashi, Go; Asanuma, Fujio; Suzuki, Noriko; Hattori, Maki; Sakamoto, Shingo; Kugimiya, Akira; Tomita, Yasuhiko; Kuwajima, Goro; Abraham, William M.; Deguchi, Masashi; Arimura, Akinori; Shichijo, Michitaka.

In: European Journal of Pharmacology, Vol. 765, 70151, 12.08.2015, p. 15-23.

Research output: Contribution to journalArticle

Takahashi, G, Asanuma, F, Suzuki, N, Hattori, M, Sakamoto, S, Kugimiya, A, Tomita, Y, Kuwajima, G, Abraham, WM, Deguchi, M, Arimura, A & Shichijo, M 2015, 'Effect of the potent and selective DP1 receptor antagonist, asapiprant (S-555739), in animal models of allergic rhinitis and allergic asthma', European Journal of Pharmacology, vol. 765, 70151, pp. 15-23. https://doi.org/10.1016/j.ejphar.2015.08.003
Takahashi, Go ; Asanuma, Fujio ; Suzuki, Noriko ; Hattori, Maki ; Sakamoto, Shingo ; Kugimiya, Akira ; Tomita, Yasuhiko ; Kuwajima, Goro ; Abraham, William M. ; Deguchi, Masashi ; Arimura, Akinori ; Shichijo, Michitaka. / Effect of the potent and selective DP1 receptor antagonist, asapiprant (S-555739), in animal models of allergic rhinitis and allergic asthma. In: European Journal of Pharmacology. 2015 ; Vol. 765. pp. 15-23.
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abstract = "Prostaglandin (PG) D2 elicits responses through either the DP1 and/or DP2 receptor. Experimental evidence suggests that stimulation of the DP1 receptor contributes to allergic responses, such that antagonists are considered to be directed therapies for allergic diseases. In this study, we demonstrate the activity of a novel synthetic DP1 receptor antagonist termed asapiprant (S-555739) for the DP1 receptor and other receptors in vitro, and assess the efficacy of asapiprant in several animal models of allergic diseases. We determined the affinity and selectivity of asapiprant for the DP1 receptor in binding assays. In the animal models of allergic rhinitis, changes in nasal resistance, nasal secretion, and cell infiltration in nasal mucosa were assessed after antigen challenge with and without asapiprant. Similarly, in the animal models of asthma, the effect of antigen challenge with and without asapiprant on antigen-induced bronchoconstriction, airway hyper-responsiveness, mucin production, and cell infiltration in lung were assessed. In binding studies, asapiprant exhibited high affinity and selectivity for the DP1 receptor. Significant suppression of antigen-induced nasal resistance, nasal secretion, and cell infiltration in nasal mucosa was observed with asapiprant treatment. In addition, treatment with asapiprant suppressed antigen-induced asthmatic responses, airway hyper-responsiveness, and cell infiltration and mucin production in lung. These results show that asapiprant is a potent and selective DP1 receptor antagonist, and exerts suppressive effects in the animal models of allergic diseases. Thus, asapiprant has potential as a novel therapy for allergic airway diseases.",
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AU - Sakamoto, Shingo

AU - Kugimiya, Akira

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