Effect of a peptide leukotriene receptor antagonist, ONO-1078, on guinea-pig models of asthma

Nakagawa, Naoki; Obata, Takaaki; Kobayashi, Tadamasa; Okada, Yutaka; Nambu, Fumio; Terawaki, Tamiya; Furuya, Toshiko; Muryobayashi, Keiko; Sawada, Masafumi; Aishita, Hideki

doi:10.1016/0014-2999(93)90139-9

Cited by 50 publications

(28 citation statements)

References 26 publications

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“…(un published data). In contrast, the cysLT-dependency of late phase response is best illustrated by the observation that cysLT antagonists more efficiently block the late phase bronchoconstriction than that in the early-phase in experimental models of bronchial asthma (12).…”

Section: Discussionmentioning

confidence: 92%

Effects of a Specific Cysteinyl Leukotriene Antagonist, Pranlukast, on Antigen-Induced Cysteinyl Leukotriene-Mediated Rhinitis in Guinea Pigs

Fujita

Yonetomi

Takeda

et al. 1997

Japanese Journal of Pharmacology

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ABSTRACT-To examine the effects of a specific cysteinyl leukotriene (cysLT) antagonist, pranlukast, on allergic rhinitis, antigen-induced rhinitis in guinea pigs was modified by pretreatment with an cyclo oxygenase inhibitor (indomethacin) followed by an H1-blocker (pyrilamine). Intranasal ovalbumin (OVA) administration in actively sensitized guinea pigs resulted in concentration-dependent increases in nasal permeability and nasal airway resistance (NAR). Although pyrilamine (1 mg/kg, i.v.) abolished these antigen-induced changes, pretreatment with indomethacin (5 mg/kg, i.v.) followed by pyrilamine enhanced these responses to a degree similar to that observed with OVA challenge alone. Analyses of nasal perfusate in indomethacin/pyrilamine-pretreated animals showed that cysLTs increased by 270.8%, whereas throm boxane B2 decreased by 88.3% as compared with those on challenged with OVA alone. Oral administration of pranlukast (1-10 mg/kg) dose-dependently prevented increases in nasal permeability and NAR of indo methacin/pyrilamine-pretreated animals. However, an anti-allergic agent, azelastine, did not affect these responses. These results indicate that pranlukast suppresses antigen-induced cysLT-mediated responses of allergic rhinitis in actively sensitized guinea pigs. A cysLT antagonist, pranlukast, may thus prevent cysLT-mediated symptoms of allergic rhinitis.Keywords: Pranlukast, Rhinitis, Leukotriene, Allergic, Ovalbumin Nasal symptoms of allergic rhinitis often display a biphasic pattern after antigen provocation.While the early-phase symptoms (up to 1 hr after antigen provoca tion) such as sneezing and rhinorrhea are transient, the late-phase symptom (4 8 hr after antigen provocation) characterized by nasal congestion is persistent (1). Media tors that have been suggested to participate in these symp toms include histamine, cyclooxygenase metabolites of arachidonic acid and cysteinyl leukotrienes (cysLTs) such as leukotriene C4, D4 and E4 (LTC4, LTD4 and LTE4), main components of the slow-reacting substance of anaphylaxis (SRS-A) (2). Among these mediators, cysLTs are of particular interest as they have been suggested to play a role in nasal congestion (3, 4), a symptom which is resistant to many therapeutic agents including current anti-histaminergics (5). Thus, agents that may antagonize or inhibit the action of cysLTs (anti-cysLTs) may be use ful in the treatment of allergic rhinitis.Although interest has focused on the therapeutic effects of anti-cysLTs against allergic rhinitis, current findings remain inconsistent. Clinical studies to evaluate the effects of anti-cysLTs on allergic rhinitis have produced controversial results (6, 7), and there is lack of an ap propriate animal model for allergic rhinitis to evaluate relevant effects of anti-cysLTs. This study was designed to examine the effects of a specific cysLT antagonist, pranlukast, which has previously been demonstrated to be a useful agent for treatment of bronchial asthma (8) with a novel model of antigen-induced rhinitis in guinea pigs. We...

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Section: Discussionmentioning

confidence: 92%

Effects of a Specific Cysteinyl Leukotriene Antagonist, Pranlukast, on Antigen-Induced Cysteinyl Leukotriene-Mediated Rhinitis in Guinea Pigs

Fujita

Yonetomi

Takeda

et al. 1997

Japanese Journal of Pharmacology

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“…23) Regarding guinea pig IAR and the LAR model, it is known that antihistamine suppresses IAR but not LAR, 24) anti-TXA 2 suppress IAR 25) and that anti-LT suppresses both IAR and LAR. 26) In addition, b2-agonists like salbutamol suppress only IAR but not LAR, indicating that IAR is mainly medi- ated by airway smooth muscle contraction.…”

Section: Discussionmentioning

confidence: 99%

Two Pharmacological Phases in Antigen-Induced Immediate Airway Response in Rats

Miyagawa

Iwasaki

Kato

et al. 2008

Biological & Pharmaceutical Bulletin

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The pharmacological profiles of antigen-induced immediate airway response (IAR) in rats are not fully understood. In this study, we established an ovalbumin (OVA)-induced IAR model using noninvasive measurement in rats, and evaluated the effects of commonly used and effective antiasthmatic drugs, i.e. ketotifen (antihistamine), pranlukast (anti-leukotriene C 4 /D 4 /E 4 (LT)), seratrodast (anti-thromboxane A 2 (TXA 2 )), salbutamol (b b2-agonist), and prednisolone (steroid). The rat IAR model exhibited an optimal rapid airway response, and salbutamol inhalation completely suppressed the IAR. Ketotifen inhibited only the quick phase (QP; the reaction from 3 to 6 min after challenge), while pranlukast and seratrodast suppressed only the early phase (EP; the reaction from 6 to 30 min after challenge). Prednisolone inhibited both QP and EP. Further, continuous administration of compound 48/80, which depletes connective tissue mast cells (CTMC), partially inhibited QP but not EP. In conclusion, these findings suggest that the pharmacological profiles of noninvasive rat IAR are similar to those of asthmatic patients, and that rat IAR exhibits additional, immunological diverse characteristics, i.e. QP caused by the exocytosis of mediators in CTMCs and EP mediated by LT and TXA 2 , which are produced by mucosal mast cells (MMCs) and possibly by other types of cells. This is the first report about the comprehensive pharmacological profiles of rodent IAR model, and these analyses of rat IAR model may help expand our understanding of the diverse mechanisms underlying human asthmatic diseases.

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“…Thus, pranlukast inhibited not only the early-phase bronchoconstriction but also several late-phase responses, including late-phase bronchoconstriction, infiltration of inflammatory cells, and airway hyper-responsiveness (Nakagawa et al, 1993;Arakida et al, 2000). These results suggest that inhibition of leukotriene action may cause the inhibition of the late-phase responses as well as the early airway response.…”

Section: Inhibition By Ta-270 Of Leukotriene Production 587mentioning

confidence: 75%

TA-270 [4-Hydroxy-1-methyl-3-octyloxy-7-sinapinoylamino-2(1 H)-quinolinone], an Anti-Asthmatic Agent, Inhibits Leukotriene Production Induced by IgE Receptor Stimulation in RBL-2H3 Cells

Ishiwara¹,

Aoki²,

Takagaki³

et al. 2003

The Journal of Pharmacology and Experimental Therapeutics

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A novel quinolinone derivative, TA-270 [4-hydroxy-1-methyl-3-octyloxy-7-sinapinoylamino-2(1H)-quinolinone], has been shown to inhibit antigen-induced asthmatic responses including the early-phase bronchoconstriction in actively sensitized guinea pigs. Here we characterized the action mechanisms of TA-270 in cellular level in vitro. In RBL-2H3 mast cells sensitized with dinitrophenol (DNP)-specific IgE, the antigen exhibited several mast cell functions, including hexosaminidase release as a marker of degranulation, production of tumor necrosis factor-␣, and production of immunologically detective leukotrienes. These antigeninduced actions were associated with the activation of several early signaling events, including inositol phosphate production reflecting phospholipase C activation and extracellular signal-regulated kinase activation. When the cells were treated with TA-270, the antigen-induced leukotriene production was almost completely suppressed, but other antigen-induced actions listed above were hardly affected. This drug also failed to affect the antigen-induced phospholipase A 2 activation as evaluated by the total release of arachidonic acid and its metabolites from the cells prelabeled with radioactive arachidonic acid. However, TA-270 clearly changed the arachidonic acid metabolic pathway. It suppressed the accumulation of 5-lipoxygenase products, including leukotrienes, but hardly affected the accumulation of cyclooxygenase products. The inhibitory action of TA-270 on leukotriene production was also observed in human neutrophils and eosinophils. We conclude that TA-270 inhibits 5-lipoxygenase activity and, thereby, suppresses the antigen-induced leukotriene production.

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Effect of a peptide leukotriene receptor antagonist, ONO-1078, on guinea-pig models of asthma

Cited by 50 publications

References 26 publications

Effects of a Specific Cysteinyl Leukotriene Antagonist, Pranlukast, on Antigen-Induced Cysteinyl Leukotriene-Mediated Rhinitis in Guinea Pigs

Effects of a Specific Cysteinyl Leukotriene Antagonist, Pranlukast, on Antigen-Induced Cysteinyl Leukotriene-Mediated Rhinitis in Guinea Pigs

Two Pharmacological Phases in Antigen-Induced Immediate Airway Response in Rats

TA-270 [4-Hydroxy-1-methyl-3-octyloxy-7-sinapinoylamino-2(1 H)-quinolinone], an Anti-Asthmatic Agent, Inhibits Leukotriene Production Induced by IgE Receptor Stimulation in RBL-2H3 Cells

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