Effect of combined leukotriene D4 and thromboxane A2 receptor antagonist on mediator-controlled resistance in guinea pigs

Arakida, Yasuhito; Ohga, Keiko; Okada, Yohei; Morio, Hiroki; Suwa, Kiyotaka; Yokota, Masami; Yamada, Toshimitsu

doi:10.1016/s0014-2999(00)00583-5

Cited by 11 publications

(11 citation statements)

References 22 publications

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“…OVA-induced bronchoconstriction was measured as previously described [16], with some modification. Guinea pigs (4 weeks) were sensitized by three intraperitoneal injections of 5 μg OVA containing 1 mg of Alum every 2 weeks.…”

Section: Ova-induced Bronchoconstriction In Sensitized Guinea Pigsmentioning

confidence: 99%

Anti-asthmatic effect of ASP3258, a novel phosphodiesterase 4 inhibitor

Kobayashi¹,

Kubo²,

Hirano³

et al. 2012

International Immunopharmacology

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Section: Ova-induced Bronchoconstriction In Sensitized Guinea Pigsmentioning

confidence: 99%

Anti-asthmatic effect of ASP3258, a novel phosphodiesterase 4 inhibitor

Kobayashi¹,

Kubo²,

Hirano³

et al. 2012

International Immunopharmacology

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“…In guinea-pig models of asthma, indomethacin has been usually used to change an asthmatic response to a state where CysLTs are largely involved (20). On the other hand, regarding the allergic rhinitis model of guinea pigs, there is only one study evaluating effects of indomethacin on nasal allergy (21).…”

Section: Discussionmentioning

confidence: 99%

Nasal Blockage Induced by Oral Administration of Non-steroidal Anti-inflammatory Drugs in a Guinea-Pig Model of Allergic Rhinitis

et al. 2007

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Abstract. To elucidate the mechanisms underlying nasal symptoms in patients with aspirin hypersensitivity, we evaluated the effects of orally administered non-steroidal anti-inflammatory drugs (NSAIDs) on the nasal patency of guinea pigs with cedar pollen-induced chronic allergic rhinitis. Indomethacin (10 mg / kg) administered 1 h before a pollen challenge amplified the antigen-induced nasal blockage. More interestingly, even in the absence of the pollen challenge, indomethacin induced nasal blockage at 30 min at 4 h after administration. However, indomethacin-induced nasal blockage was not provoked in non-sensitized animals. Another NSAID, diclofenac (30 mg / kg), also evoked nasal blockage, but unexpectedly, aspirin (500 mg / kg) did not affect nasal patency. Indomethacin-induced nasal blockage was unaffected by a cysteinyl leukotriene receptor (CysLT 1 receptor) antagonist, pranlukast (30 mg / kg, p.o.), or by prostaglandin E 2 (10 −3 M, intranasal), suggesting that the nasal blockage may not be due to hyperproduction of cysteinyl leukotrienes or inhibition of prostaglandin E 2 production. These results indicate that the indomethacin-induced nasal blockage may not be an identical phenomena to airway symptoms in aspirin hypersensitivity patients. However, because chronic nasal inflammation is indispensable for the development of nasal blockage, indomethacin-induced nasal blockage may become a clue to elucidate new mechanisms underlying hypersensitivity to NSAIDs.

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“…Since cysLTs and TXA 2 play different roles in the development and onset of asthma, inhibition of multiple pathways may yield more potent therapeutic effects. In fact, the therapeutic benefits of cysLT receptor and TP dual antagonists have been reported in guinea pig models [21,22] . These reports focused mainly on respiratory function, but there are few reports that evaluated the therapeutic effects of these antagonists by histopathological methods.…”

Section: Introductionmentioning

confidence: 99%

The Effects of Inhaled KP-496, a Novel Dual Antagonist for Cysteinyl Leukotriene Receptor and Thromboxane A<sub>2</sub> Receptor, on Allergic Asthmatic Responses in Guinea Pigs

et al. 2009

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Aims: The aim of this study was to evaluate the effects of inhaled KP-496, a novel dual antagonist for cysteinyl leukotriene receptor 1 and thromboxane A₂ receptor, on the allergic asthmatic responses in guinea pigs. Methods: Actively sensitized animals were repeatedly exposed to antigen, and KP-496 (0.01 and 0.1%) was inhaled for 5 min before every antigen exposure. After evaluating the effects of KP-496 on asthmatic responses, such as immediate and late asthmatic response (IAR and LAR) and airway hyperresponsiveness (AHR), histopathological analyses of the lungs of asthmatic animals were made. Results: KP-496 significantly inhibited both antigen-induced LAR and AHR to acetylcholine, and slightly inhibited antigen-induced IAR. Furthermore, histopathological analyses of the lungs of the asthmatic animals demonstrated the following: (1) KP-496 suppressed infiltration of eosinophils around airway smooth muscle, (2) KP-496 suppressed airway epithelial hypertrophy, and (3) KP-496 suppressed increased mucus production in the airway. Conclusion: In addition to suppression of LAR and AHR, our findings demonstrated that KP-496 inhibits features of airway inflammation. Since these broad ameliorative effects of KP-496 on asthmatic pathology are thought to result from the inhibition of multiple chemical mediators, KP-496 will be a potent agent in the treatment of bronchial asthma.

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Effect of combined leukotriene D4 and thromboxane A2 receptor antagonist on mediator-controlled resistance in guinea pigs

Cited by 11 publications

References 22 publications

Anti-asthmatic effect of ASP3258, a novel phosphodiesterase 4 inhibitor

Anti-asthmatic effect of ASP3258, a novel phosphodiesterase 4 inhibitor

Nasal Blockage Induced by Oral Administration of Non-steroidal Anti-inflammatory Drugs in a Guinea-Pig Model of Allergic Rhinitis

The Effects of Inhaled KP-496, a Novel Dual Antagonist for Cysteinyl Leukotriene Receptor and Thromboxane A<sub>2</sub> Receptor, on Allergic Asthmatic Responses in Guinea Pigs

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