Abstract | BACKGROUND:
Prostaglandin (PG) D(2) is the major cylooxygenase metabolite released by mast cells upon allergen stimulation, and elicits responses through either the prostanoid DP1 receptor and/or the chemoattractant receptor homologous molecule expressed on T-helper type 2 (Th2) cells (CRTH2/DP2). Experimental evidence suggests that stimulation of one or both these receptors contributes to asthma pathophysiology. OBJECTIVE: METHODS: PGD(2)-induced cyclic adenosine monophosphate (cAMP) production in platelet-rich plasma was used to establish the in vitro efficacy of S-5751. In vivo, sheep naturally allergic to Ascaris suum were challenged with an aerosolized antigen with and without S-5751 treatment (given 4 days before and for 6 days after the challenge). RESULTS:
S-5751 inhibited PGD(2)-induced cAMP production in platelet-rich plasma with an IC(50) value of 0.12 microm. S-5751 at 30 mg/kg, but not at 3 mg/kg, reduced the early bronchoconstriction and inhibited the late bronchoconstriction. AHR and inflammatory cell infiltration in bronchoalveolar lavage fluid at days 1 and 7 were also inhibited with the 30 mg/kg dose. The responses observed with S-5751 at 30 mg/kg were comparable with those with montelukast treatment (0.15 mg/kg, twice a day, intravenous); however, S-5751 did not block inhaled leukotrieneD(4)-induced broncoconstriction. CONCLUSION:
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Authors | M Shichijo, A Arimura, Y Hirano, K Yasui, N Suzuki, M Deguchi, W M Abraham |
Journal | Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology
(Clin Exp Allergy)
Vol. 39
Issue 9
Pg. 1404-14
(Sep 2009)
ISSN: 1365-2222 [Electronic] England |
PMID | 19486034
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- 7(2-(5-hydroxybenzo(b)thiophen-3-ylcarbonylamino)-10-norpinan-3-yl)hept-5-enoic acid
- Acetates
- Allergens
- Anti-Asthmatic Agents
- Cyclopropanes
- Quinolines
- Receptors, Immunologic
- Receptors, Prostaglandin
- Sulfides
- Thiophenes
- Cyclic AMP
- montelukast
- Prostaglandin D2
- prostaglandin D2 receptor
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Topics |
- Acetates
(pharmacology)
- Allergens
(toxicity)
- Animals
- Anti-Asthmatic Agents
(pharmacology)
- Asthma
(chemically induced, drug therapy, metabolism)
- Bronchoalveolar Lavage Fluid
- Bronchoconstriction
(drug effects)
- Cyclic AMP
(metabolism)
- Cyclopropanes
- Disease Models, Animal
- Dose-Response Relationship, Drug
- Female
- Humans
- Prostaglandin D2
(metabolism)
- Quinolines
(pharmacology)
- Receptors, Immunologic
(antagonists & inhibitors, metabolism)
- Receptors, Prostaglandin
(antagonists & inhibitors, metabolism)
- Sulfides
- Thiophenes
(pharmacology)
- Time Factors
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