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 language | English (US) |
|---|---|
| Article number | 70151 |
| Pages (from-to) | 15-23 |
| Number of pages | 9 |
| Journal | European Journal of Pharmacology |
| Volume | 765 |
| DOIs | |
| State | Published - Aug 12 2015 |
| Externally published | Yes |
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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 journal › Article
}
TY - JOUR
T1 - Effect of the potent and selective DP1 receptor antagonist, asapiprant (S-555739), in animal models of allergic rhinitis and allergic asthma
AU - Takahashi, Go
AU - Asanuma, Fujio
AU - Suzuki, Noriko
AU - Hattori, Maki
AU - Sakamoto, Shingo
AU - Kugimiya, Akira
AU - Tomita, Yasuhiko
AU - Kuwajima, Goro
AU - Abraham, William M.
AU - Deguchi, Masashi
AU - Arimura, Akinori
AU - Shichijo, Michitaka
PY - 2015/8/12
Y1 - 2015/8/12
N2 - 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.
AB - 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.
KW - Allergic rhinitis
KW - Asapiprant
KW - Nasal congestion
KW - Prostaglandin D<inf>2</inf>
KW - Synthetic DP<inf>1</inf> receptorantagonist
UR - http://www.scopus.com/inward/record.url?scp=84939558418&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84939558418&partnerID=8YFLogxK
U2 - 10.1016/j.ejphar.2015.08.003
DO - 10.1016/j.ejphar.2015.08.003
M3 - Article
AN - SCOPUS:84939558418
VL - 765
SP - 15
EP - 23
JO - European Journal of Pharmacology
JF - European Journal of Pharmacology
SN - 0014-2999
M1 - 70151
ER -