Inhibitory effect of inhaled procaterol on anaphylactic bronchoconstriction and thromboxane <i>A</i><sub>2</sub> production in guinea‐pigs

Fujimura, Masaki; Sakamoto, Sayuri; Nishi, Kiyoto; Saito, Motoyasu; Miyake, Yohei; Matsuda, Tamotsu

doi:10.1111/j.1365-2222.1991.tb00829.x

Cited by 24 publications

(17 citation statements)

References 22 publications

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“…In addition, TxA2 may, in this species, be one of the final pathways of airflow obstruction and airway plasma exudation induced by platelet activating factor (Tokuyama et al, 1991) and bradykinin Kawikova et al, 1992). In guinea-pigs, allergeninduced airflow obstruction is mediated in part via TxA2 production (Beasley et al, 1989;Arakawa et al, 1993), and an increased level of TxB2 is found in bronchoalveolar lavage after allergen challenge (Fujimura et al, 1991).…”

Section: Introductionmentioning

confidence: 99%

Leukotriene D₄‐ and prostaglandin F_2α‐induced airflow obstruction and airway plasma exudation in guinea‐pig: role of thromboxane and its receptor

Arakawa

Lötvall

Kawikova

et al. 1993

British J Pharmacology

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1 We studied the effects of a thromboxane A2 receptor (TP receptor) antagonist, i.v.) and a selective thromboxane (Tx) synthetase inhibitor, OKY-046 (30mgkg-1, i.v.), on airway responses induced by leukotriene D4 (LTD4; 0.2 nmol) or prostaglandin F2a, (PGF2,; 20 nmol) instilled via the airways route to anaesthetized guinea-pigs. For a comparison, airway responses to a TxA2-mimetic, U-46619 (0.02 nmol) were also studied. We measured both lung resistance (RL) to monitor airflow obstruction, and extravasation of Evans Blue dye to quantify airway plasma exudation. 2 Instilled LTD4 into the tracheal lumen induced an immediate peak and subsequently persistent increase in RL and produced a large amount of extravasation of Evans Blue dye at all airway levels. Both 605 and OKY-046 significantly attenuated the persistent increase in RL following the immediate response and reduced LTD4-induced extravasation of Evans Blue dye in the trachea and proximal intrapulmonary airway. Instilled LTD4 produced significant increases in immunoreactive TxB2 in bronchoalveolar lavage fluid obtained 1.5 min after instillation of LTD4.3 Instilled PGF2. into the tracheal lumen induced an immediate increase in RL which peaked at approximately 15 s. We also observed a delayed sustained increase in RL, reaching a second peak at approximately 4 min. PGF2, produced small but significant increases in the amount of Evans Blue dye at all airway levels. As with PGF,, instillation of U-46619 produced a biphasic increase in RL and extravasation of Evans Blue dye. The potency of PGFu, in inducing these airway responses was about 1000 times less than U-46619. 605 abolished both the immediate and the delayed increase in RL after PGF20, and also blocked PGF2,-induced extravasation of Evans Blue dye. However, OKY-046 had no inhibitory effects on these responses. 4 We conclude that airflow obstruction and airway plasma exudation induced by instilled LTD4 is, in part, mediated via TxA2 generation and subsequent activation of TP-receptors. On the other hand, instilled PGF2., while inducing similar responses, does so primarily by direct activation of TP receptors, rather than via TxA2 generation.

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Section: Introductionmentioning

confidence: 99%

Leukotriene D₄‐ and prostaglandin F_2α‐induced airflow obstruction and airway plasma exudation in guinea‐pig: role of thromboxane and its receptor

Arakawa

Lötvall

Kawikova

et al. 1993

British J Pharmacology

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“…The resulting ID 50 or IC 50 values showed that cilostazol powder was somewhat less inhibitory regarding antigen–induced bronchoconstriction than histamine–induced bronchoconstriction (ID 50 of 60.4µg against antigen vs. 7.0 µg against histamine), while KF19514 solution was more active against antigen–induced bronchoconstriction than against histamine–induced bronchoconstriction (IC 50 of 0.40 against antigen vs. 2.81 µg/ml against histamine). The inhibitory effects of cilostazol and KF–19514 against histamine–induced bronchoconstriction are relatively weak compared with that of a β 2 –agonist procaterol with an IC 50 of less than 0.5 µg/ml previously shown by us [28]. …”

Section: Discussionmentioning

confidence: 99%

“…Since Pao increased immediately after antigen and histamine inhalation and the bronchodilator procaterol almost completely inhibited the increases in Pao [28], it is likely that the increase in Pao is indicative of bronchoconstriction in our experimental system.…”

Section: Discussionmentioning

confidence: 99%

Bronchoprotective Effect of an Intrabronchial Administration of Cilostazol Powder and a Nebulized PDE1 and PDE4 Inhibitor KF19514 in Guinea Pigs

Fujimura¹,

Tachibana²,

Myou³

et al. 1998

Int Arch Allergy Immunol

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Background: Both oral and intravenous inhibitors of cyclic nucleotide phosphodiesterase (PDE) 3 and PDE4 have been shown to have bronchodilator and/or pulmonary antiallergic effects but their adverse effects limit the clinical use. The purpose of the present study was to assess the bronchoprotective effect of intrabronchial administration of a selective PDE3 inhibitor, 6–[4–(1–cyclohexyl–1H–tetrazol–5–yl)butoxy]–3,4–dihydro–2(1H)–quinolinone (cilostazol), in dry power form which is proposed to be desirable rather than propellant–driven metered–dose inhalers. Methods: Effect of an intrabronchial administration of cilostazol powder on aerosolized histamine– and antigen–induced leukotriene–mediated bronchoconstriction were examined in anesthetized and artificially ventilated guinea pigs, in comparison with the effects of ultrasonically nebulized 5–phenyl–3–(3–pyridyl)methyl–3H–imidazo[4,5–c] [1,8] naphthyridin–4(5H)–one (KF19514), a selective PDE1/4 inhibitor. Results: Cilostazol powder and KF19514 solution inhibited histamine– and antigen–induced bronchoconstriction in a dose–dependent manner. When assessing the resulting ED₅₀ values, the activity of cilostazol powder against antigen–induced broncho–constriction was weaker than its antagonism of histamine–induced bronchoconstriction (60.4 vs. 7.0 μg), while those of KF19514 were the opposite (0.40 vs. 2.81 μg/ml). Conclusion: These results suggest that intrabronchially administered cilostazol powder has a bronchodilator effect, and ensure that PDE4 inhibitors have an antiallergic activity in addition to their bronchodilator effect.

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“…Since Pao increased immediately after antigen and histamine inhalation and the bronchodilator procaterol almost completely inhibited the increases in Pao [17], it is likely that the increase in Pao is indicative of bronchoconstriction in our experimental system.…”

Section: Discussionmentioning

confidence: 99%

Role of leukotriene B4 in bronchial hyperresponsiveness induced by interleukin-8

Fujimura¹,

Xiu²,

Tsujiura³

et al. 1998

Eur Respir J

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Repeated intranasal administration of interleukin 8 (IL-8) induces bronchial hyperresponsiveness (BHR) accompanied by lower airway neutrophil accumulation (ANA) in guinea-pigs. Leukotriene B4 (LTB4) is a chemotactic factor for neutrophils. To elucidate whether LTB4 and neutrophil elastase are involved in the IL-8-induced BHR and ANA, the effects of a LTB4 antagonist (ONO-4057) and a neutrophil elastase inhibitor (ONO-5046) on the responses were examined. IL-8 (5 microg x kg[-1]) was administered intranasally to guinea-pigs twice weekly for 3 weeks. One day after the last administration, animals were anaesthetized and artificially ventilated through tracheal cannulae, and lateral pressure at the tracheal cannula (Pao) was measured as an overall index of airway responses to inhaled histamine. ONO-4057 (2 or 20 mg x kg[-1]) or ONO-5046 (30 or 300 mg x kg[-1]) was administered intraperitoneally 24 and 1 h before anaesthesia. ONO-4057, but not ONO-5046, significantly inhibited the IL8-induced BHR and ANA, assessed by bronchoalveolar lavage, in a dose-dependent manner. These findings suggest that interleukin 8 causes bronchial hyperresponsiveness and airway neutrophil accumulation in guinea-pigs in vivo. In part this appears to be due to release of leukotriene B4, whereas it may not be mediated by neutrophil elastase.

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Inhibitory effect of inhaled procaterol on anaphylactic bronchoconstriction and thromboxane A₂ production in guinea‐pigs

Cited by 24 publications

References 22 publications

Leukotriene D₄‐ and prostaglandin F_2α‐induced airflow obstruction and airway plasma exudation in guinea‐pig: role of thromboxane and its receptor

Leukotriene D₄‐ and prostaglandin F_2α‐induced airflow obstruction and airway plasma exudation in guinea‐pig: role of thromboxane and its receptor

Bronchoprotective Effect of an Intrabronchial Administration of Cilostazol Powder and a Nebulized PDE1 and PDE4 Inhibitor KF19514 in Guinea Pigs

Role of leukotriene B4 in bronchial hyperresponsiveness induced by interleukin-8

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Inhibitory effect of inhaled procaterol on anaphylactic bronchoconstriction and thromboxane A2 production in guinea‐pigs

Cited by 24 publications

References 22 publications

Leukotriene D4‐ and prostaglandin F2α‐induced airflow obstruction and airway plasma exudation in guinea‐pig: role of thromboxane and its receptor

Leukotriene D4‐ and prostaglandin F2α‐induced airflow obstruction and airway plasma exudation in guinea‐pig: role of thromboxane and its receptor

Bronchoprotective Effect of an Intrabronchial Administration of Cilostazol Powder and a Nebulized PDE1 and PDE4 Inhibitor KF19514 in Guinea Pigs

Role of leukotriene B4 in bronchial hyperresponsiveness induced by interleukin-8

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Inhibitory effect of inhaled procaterol on anaphylactic bronchoconstriction and thromboxane A₂ production in guinea‐pigs

Leukotriene D₄‐ and prostaglandin F_2α‐induced airflow obstruction and airway plasma exudation in guinea‐pig: role of thromboxane and its receptor

Leukotriene D₄‐ and prostaglandin F_2α‐induced airflow obstruction and airway plasma exudation in guinea‐pig: role of thromboxane and its receptor