Effects of CS-518, a thromboxane synthase inhibitor, on eosinophil function

Itoh, Kazuhiro; Mukaiyama, Osamu; Satoh, Yumiko; Yamaguchi, Takeshi; Iizuka, Yoshio

doi:10.1016/0014-2999(93)90989-u

Cited by 15 publications

(12 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This is consistent with the previous observation in which capsaicin pretreatment did not affect increase in BALF cell counts after antigen inhalation in sensitized guinea pigs [32]. We have previously observed that ovalbumin-induced eosinophil accumulation is inhibited by thromboxane synthase inhibitor and platelet-activating factor antagonist in a guinea pig model of mild asthma [46]. These observations suggest that the main mediator of the development of eosinophil accumulation in animal models of mild asthma is a substance unrelated to neurokinins, e.g.…”

Section: Discussionsupporting

confidence: 92%

Greater Involvement of Neurokinins Found in Guinea Pig Models of Severe Asthma Compared with Mild Asthma

Mukaiyama

Morimoto²,

Nosaka³

et al. 2004

Int Arch Allergy Immunol

Self Cite

View full text Add to dashboard Cite

Background: Involvement of neurokinins in asthma has been previously pointed out by several reports. However, the relationship between neurokinins and the severity of asthma has remained unclear. We developed a model of mild asthma (model I) and severe asthma (model II) in guinea pigs, and investigated the function of neurokinins in both models. Methods: In models I and II, systemically sensitized guinea pigs were made to inhale ovalbumin once and three times, respectively. Substance P (SP) and neurokinin A (NKA) concentrations in the bronchoalveolar lavage fluid (BALF) were measured in models I and II. Then, the effects of a capsaicin pretreatment, which depletes neurokinins, in both animal models on airway narrowing induced by the last ovalbumin inhalation, airway hyperresponsiveness to inhaled methacholine, and eosinophil accumulation in BALF, were investigated. Results: SP concentration tended to increase and the NKA concentration increased significantly in model II, but not in model I. Capsaicin pretreatment significantly inhibited the late bronchial response that was observed 2–6 h after the last ovalbumin inhalation, airway hyperresponsiveness and eosinophil accumulation in model II. On the other hand, it had no effects on the responses in model I. Conclusion: It is suggested that the more severe the disease, the greater the involvement of neurokinins.

show abstract

Section: Discussionsupporting

confidence: 92%

Greater Involvement of Neurokinins Found in Guinea Pig Models of Severe Asthma Compared with Mild Asthma

Mukaiyama

Morimoto²,

Nosaka³

et al. 2004

Int Arch Allergy Immunol

Self Cite

View full text Add to dashboard Cite

show abstract

“…in the experimental model o f im mediate asthmatic response [18]. Furthermore, CS-518 in hibited antigen-induced eosinophil accumulation and eosinophil hypodensity in BALF in vivo, and inhibited eosi nophil peroxidase release and eosinophil chemotaxis to PAF in vitro [12].…”

Section: Introductionmentioning

confidence: 95%

“…1) is a potent, long-acting and selective in hibitor o f TXA2 synthase [16,17] discovered in our labora tories. This compound not only inhibited TX production but also enhanced prostaglandin (PG) E2 and PGI2 production in the bronchoalveolar tissue of actively sensitized guinea pigs and guinea pig eosinophils [12,15]. CS-518 also inhib ited LTD4-induced TXA2 production in the bronchoalveo lar tissue of normal guinea pigs and guinea pig eosinophils [12,15].…”

Section: Introductionmentioning

confidence: 97%

“…Inhalation ofepithiometharo-TXA2 or U-46619, both TXA: mimetic agents, or LTC4 or LTE4 is reported to cause an increase in airway response to acetyl choline, histamine, leukotriene D4 or vagal nerve stimula tion in animals and humans [8 11], Both a TXA2 synthase inhibitor and an LT antagonist were reported to inhibit anti gen-induced eosinophil accumulation in actively sensitized guinea pigs [12,13]. We have also reported that inhaled pep tide leukotriene induced selective eosinophil accumulation in normal guinea pigs [14], Peptide leukotrienes are report ed to induce TXA: production in bronchoalveolar tissue [15] and eosinophils [12] in guinea pigs in vitro. These re sults suggest that TXA2 (and LTC4) are significantly in volved not only in the development of AIIR but also in eosi nophil accumulation, and play an important role in aggrava tion of asthma.…”

Section: Introductionmentioning

confidence: 99%

“…This compound not only inhibited TX production but also enhanced prostaglandin (PG) E2 and PGI2 production in the bronchoalveolar tissue of actively sensitized guinea pigs and guinea pig eosinophils [12,15]. CS-518 also inhib ited LTD4-induced TXA2 production in the bronchoalveo lar tissue of normal guinea pigs and guinea pig eosinophils [12,15]. CS-518 suppressed the bronchoconstriction caused by slow reacting substances of anaphylaxis (SRS-A: mainly endogenous peptide leukotrienes) and antigen-induced hy perresponsiveness to the intravenous injection o f methacholine (IDj0: 3 nig/kg p.o.)…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Effects of a Thromboxane Synthase Inhibitor (CS-518) on the Eosinophil-Dependent Late Asthmatic Response and Airway Hyperresponsiveness in Guinea Pigs

Itoh¹,

Takahashi²,

Mukaiyama³

et al. 1996

Int Arch Allergy Immunol

Self Cite

View full text Add to dashboard Cite

The effects of CS-518, a thromboxane A₂ synthase inhibitor, on antigen-induced dual bronchial responses, airway hyperresponsiveness (AHR) and airway eosinophilia were investigated in an experimental guinea pig model of the late asthmatic response. Oral CS-518 (1 and 10 mg/kg) inhibited immediate and late asthmatic responses dose-dependently. It also inhibited AHR and eosinophil accumulation after antigen challenge. Therefore, thromboxane A₂ is possibly involved in development of the late asthmatic response and AHR, and CS-518 was inferred to inhibit these via inhibition of eosinophil accumulation and thromboxane production.

show abstract

The effect of a thromboxane A2 receptor antagonist BAY-u-3405 on experimental allergic reactions

et al. 1995

View full text Add to dashboard Cite

Effects of CS-518, a thromboxane synthase inhibitor, on eosinophil function

Cited by 15 publications

References 41 publications

Greater Involvement of Neurokinins Found in Guinea Pig Models of Severe Asthma Compared with Mild Asthma

Greater Involvement of Neurokinins Found in Guinea Pig Models of Severe Asthma Compared with Mild Asthma

Effects of a Thromboxane Synthase Inhibitor (CS-518) on the Eosinophil-Dependent Late Asthmatic Response and Airway Hyperresponsiveness in Guinea Pigs

The effect of a thromboxane A2 receptor antagonist BAY-u-3405 on experimental allergic reactions

Contact Info

Product

Resources

About