The effect of leukotriene antagonists, lipoxygenase inhibitors and selected standards on leukotriene-mediated allergic bronchospasm in guinea pigs

Kreutner, William; Sherwood, J; Rizzo, Charles A.

doi:10.1007/bf01967398

Cited by 21 publications

(9 citation statements)

References 64 publications

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“…It has been reported that antigen-induced cysLT mediated increases in bronchial airway resistance display slower onset (1 to 2 min after antigen challenge) and de velopment when compared with those induced by anti gens alone in guinea pigs (9), depicting the characteristic responses of cysLTs as SRS-A (9, 13). However, we did not observe such delays in pyrilamine/indomethacin pretreated animals, at least within the observation period of this study.…”

Section: Discussionmentioning

confidence: 99%

“…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 thus employed pretreatment with indomethacin followed by pyrilamine to pharmacologically modify and develop an antigen-induced cysLT-mediated response in guinea pigs (9).…”

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confidence: 99%

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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: 99%

mentioning

confidence: 99%

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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“…In sensitized guinea pigs pretreated with indomethacin, pyrilamine and proprano lol, antigen challenge causes slowly developing and sustained bronchoconstriction indicative of a SRS-A response. This response is prevented by LT antagonists and lipoxygenase inhibitors (20,21, this paper). In the present study, the LT antagonists FPL55712 and LY171883 gra dually reversed antigen-induced bronchocon striction, but the lipoxygenase inhibitor pheni done, which was prophylactically effective, did not have any significant effect.…”

Section: Discussionmentioning

confidence: 81%

Reversing Effect of Anti-Asthmatic Drugs on Bronchoconstriction Induced by Antigen Challenge and Histamine in Anesthetized Guinea Pigs.

et al. 1992

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We performed an in vivo evaluation of bronchodilation using a model of antigen-induced bronchoconstriction in anesthetized guinea pigs pretreated with in domethacin, pyrilamine and propranolol, and the results were compared with those for the histamine-induced response. Test drugs were administered intravenously when the antigen or histamine response reached its peak. Leukotriene (LT) D4 antagonists, FPL55712 and LY171883, gradually reduced the antigen-induced response, whereas the lipoxygenase inhibitor phenidone had no such effect. The bronchodilator theophylline rapidly reduced the antigen-induced response, and the adenylate cyclase activator forskolin had a similar effect. The following drugs also had no effect: nifedi pine (calcium-channel antagonist), cromakalim (potassium-channel opener), amlex anox and disodium cromoglycate: DSCG (anti-allergic drugs), OKY-046 (thrombox ane A2 synthetase inhibitor), and dapsone (anti-inflammatory drug). Theophylline, the beta-adrenoceptor agonist salbutamol and the histamine H1-blocker pyrilamine had only a small reversing effect on histamine-induced bronchoconstriction. These re sults suggest that antigen-, but not histamine-, induced bronchoconstriction in anesthe tized guinea pigs is a useful in vivo model for evaluating the bronchodilating effect of anti-asthmatic drugs.Bronchodilators, theophylline and beta adrenoceptor agonists are widely used in the therapy of asthma (1, 2). Theophylline inhibits antigen and agonists-induced bronchospasm in guinea pigs (3, 4), and it also has an anti allergic effect in rats (5, 6). Similarly, beta adrenoceptor agonists, salbutamol and iso proterenol, and the adenylate cyclase activator forskolin have anti-asthmatic and anti-allergic activity (7,8). Calcium-channel antagonists (9, 10) and potassium channel openers (11-13) also exhibit bronchodilating effects in the guinea pig, and anti-allergic drugs, DSCG and amlexanox (14), and the TXA2 synthetase in hibitor OKY-046 (15) inhibit antigen-induced bronchospasm in the guinea pig. However, the bronchodilating effect of these drugs on bron choconstriction in vivo have not been investi gated in detail.The purpose of the present study was to de velop an in vivo system for examining the bronchodilating effect of anti-asthmatic drugs. Therefore, we examined the reversing effects of anti-asthmatic drugs on antigen-induced bronchoconstriction in anesthetized guinea pigs, because antigen causes slowly developing and sustained bronchoconstriction in sensitized guinea pigs pretreated with indomethacin,

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“…), to highlight the lipoxygenase pathway; and 10 min before OA challenge, with mepyramine maleate (0.5 mg·kg -1 i.v. ), to block H 1 receptors [14]. The guinea-pigs were then challenged with an aerosol of 1% OA in saline for 5 s, delivered by the nebulizer (Devilbiss Pulmosonic), with an output of 1 mL·min -1 and a particle size of 0.6-15 µm; the nebulizer was connected in series with the ventilatory pump.…”

Section: Leukotriene-mediated Allergic Bronchospasm In Sensitized Guimentioning

confidence: 99%

“…The guinea-pigs were then challenged with an aerosol of 1% OA in saline for 5 s, delivered by the nebulizer (Devilbiss Pulmosonic), with an output of 1 mL·min -1 and a particle size of 0.6-15 µm; the nebulizer was connected in series with the ventilatory pump. This challenge provoked a leukotriene-dependent bronchoconstriction, which was measured as an increase in PIP [14].…”

Section: Leukotriene-mediated Allergic Bronchospasm In Sensitized Guimentioning

confidence: 99%

Effects of moguisteine, a peripheral nonnarcotic antitussive agent, on airway inflammation in guinea-pigs in vivo

Gallico¹,

Oggioni²,

Rosa³

et al. 1996

Eur Respir J

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Cough is a common symptom of respiratory diseases associated with irritation or inflammation of the airways, and symptomatic antitussive drugs are frequently prescribed to control an abnormal cough reflex. Our aim was to evaluate the effects of moguisteine, a novel, peripheral, nonnarcotic antitussive agent, on airway inflammation induced in guinea-pigs with a variety of stimuli.These stimuli included exposure to tobacco smoke for 10 min, to elicit airway hyperreactivity, eosinophil recruitment in bronchoalveolar lavage (BAL), airway epithelial damage and plasma exudation; graded platelet-activating factor (PAF) infusion (600 ng·kg -1 over one h), to induce airway hyperreactivity; 2% ovalbumin (OA) aerosol challenge in 1% OA-sensitized animals, to induce late-phase (17 and 72 h) airway leucocyte accumulation. We also assessed the activity of moguisteine on plasma leakage induced by capsaicin, on bronchoconstriction induced by acetylcholine (ACh), histamine (H) and PAF, and on leukotriene mediated allergic bronchospasm in OA-sensitized guinea-pig.Moguisteine (p.o. and i.m.) and dexamethasone (p.o. and i.m.) dose-dependently reduced tobacco smoke-induced bronchial hyperreactivity. Moguisteine and dexamethasone abolished eosinophil recruitment in BAL, prevented the sloughing of the epithelium and significantly reduced airway microvascular leakage. Both agents were also highly effective in reducing bronchial hyperreactivity elicited by PAF infusion. In addition, moguisteine was active in inhibiting airway neutrophil and eosinophil accumulation in BAL observed 17 and 72 h after OA challenge in sensitized guinea-pigs. In contrast to dexamethasone, moguisteine did not prevent capsaicin-induced plasma leakage. It was also ineffective against bronchoconstriction as induced by ACh, H, and PAF and failed to inhibit leukotriene-dependent bronchospasm.Our data suggest that moguisteine represents an antitussive compound endowed with interesting airway anti-inflammatory properties in guinea-pigs in vivo. Its mechanism of action remains to be elucidated.

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The effect of leukotriene antagonists, lipoxygenase inhibitors and selected standards on leukotriene-mediated allergic bronchospasm in guinea pigs

Cited by 21 publications

References 64 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

Reversing Effect of Anti-Asthmatic Drugs on Bronchoconstriction Induced by Antigen Challenge and Histamine in Anesthetized Guinea Pigs.

Effects of moguisteine, a peripheral nonnarcotic antitussive agent, on airway inflammation in guinea-pigs in vivo

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