The effect of Paf antagonists on bronchial hyperresponsiveness induced by Paf, propranolol or indomethacin

Dixon, Emma; Wilsoncroft, P.; Robertson, D. N.; Page, Clive

doi:10.1111/j.1476-5381.1989.tb12008.x

Cited by 20 publications

(2 citation statements)

References 26 publications

(31 reference statements)

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“…Neither platelet depletion nor co-administration of ginkgolide B, a selective antagonist of PAF, diminished the hyperreactivity that resulted from infusion of (± )isoprenaline. These characteristics distinguish hyperreactivity due to (± )isoprenaline from that produced by PAF, a conclusion that can be extended to (± )propranolol (Dixon, Wilsoncroft, Robertson & Page, 1989). Such distinction has been reinforced by the effect of vagal section.…”

Section: Isoprenaline-induced Airway Hyperreactivitymentioning

confidence: 86%

Increased airway reactivity in the guinea‐pig follows exposure to intravenous isoprenaline.

Sanjar¹,

Kristersson²,

Mazzoni³

et al. 1990

The Journal of Physiology

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1. Intravenous infusion of (+/‐) isoprenaline (1‐100 micrograms kg‐1 h‐1) enhanced airway responses (resistance, RL; and compliance, Cdyn) to histamine (1.0‐1.8 micrograms kg‐1) and bombesin (100‐240 ng kg‐1), whereas airway responses to vagal stimulation remained unchanged. 2. Bilateral vagotomy before intravenous infusion of (+/‐)isoprenaline (100 micrograms kg‐1 h‐1) prevented development of airway hyperreactivity to histamine or bombesin, yet vagotomy after infusion of isoprenaline was without effect. 3. Prior treatment with atropine (1 mg kg‐1) did not influence the capacity of (+/‐)isoprenaline (100 micrograms kg‐1 h‐1) to increase airway reactivity to bombesin. 4. Despite a 500‐fold difference in spasmolytic potency in vivo, infusion of (+)isoprenaline (100 micrograms kg‐1 h‐1) or (‐)isoprenaline (100 micrograms kg‐1 h‐1) increased reactivity of the airways to histamine or bombesin to a comparable extent. 5. Neither adrenaline (100 micrograms kg‐1 h‐1) nor forskolin (600 micrograms kg‐1 h‐1) increased reactivity of the airways to histamine or bombesin. 6. Intravenous infusion of dopamine (100 micrograms kg‐1 h‐1) or noradrenaline (100 micrograms kg‐1 h‐1) increased reactivity of the airways to histamine or bombesin. 7. Intravenous infusion of (+/‐) propranolol (100 micrograms kg‐1 h‐1) increased reactivity of the airways to histamine or bombesin which was partially inhibited by bilateral vagal section. 8. Depletion of circulating platelets by lytic anti‐platelet serum or concomitant infusion of an antagonist of platelet‐activating factor (PAF), ginkgolide B (1 mg kg‐1 h‐1) did not diminish the capacity of (+/‐)isoprenaline (100 micrograms kg‐1 h‐1) to induce hyperreactivity of the airways to histamine or bombesin. 9. These observations indicate that (+/‐)isoprenaline can induce airway hyper‐reactivity by a mechanism unrelated to beta‐adrenoceptor activation, but which is dependent upon intact vagus nerves.

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Section: Isoprenaline-induced Airway Hyperreactivitymentioning

confidence: 86%

Increased airway reactivity in the guinea‐pig follows exposure to intravenous isoprenaline.

Sanjar¹,

Kristersson²,

Mazzoni³

et al. 1990

The Journal of Physiology

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“…Furthermore, PAF given intravenously or by inhalation has been shown to produce bronchial hyperreactivity to a range of spasmogens in guinea-pigs (Coyle et al 1988;Underwood et al 1992). The development of the bronchial hyperreactivity has been reported to be inhibited by treatment with a variety of established or potential anti-asthma drugs including the PAF antagonists WEB 2086, BN 52021 and RP 59227 (Dixon et al 1989;Underwood et al 1992). Similarly, bronchial hyperreactivity to several spasmogens has been demonstrated in sensitized guineapigs challenged with the antigen ovalbumin (Coyle et al 1988;Sanjar et al 1990;Underwood et al 1992).…”

Section: Introductionmentioning

confidence: 95%

The effect of the selective PAF antagonist CIS-19 on PAF- and antigen-induced bronchoconstriction, microvascular leakage and bronchial hyperreactivity in guinea-pigs

Lin

Ishii

et al. 1997

Naunyn-Schmiedeberg's Arch Pharmacol

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We investigated the effects of a novel platelet-activating factor (PAF) receptor antagonist, CIS-19 [cis-2-(3, 4-dimethoxyphenyl)-6-isopropoxy-7-methoxy-1-(N-methyl-formamido)-1, 2, 3, 4-tetrahydronaphthalene], on PAF-, histamine-, substance P- and antigen-induced bronchoconstriction and microvascular leakage, as well as PAF- and antigen-induced bronchial hyperreactivity to methacholine in urethane-anesthetized guinea-pigs. Administration of CIS-19 (0.5-5 mg/kg, i.v.) inhibited the increase in lung resistance induced by PAF (30 ng/kg, i.v.) in a dose-dependent manner, but failed to inhibit the increase induced by histamine (30 micrograms/kg, i.v.) or substance P (6.5 micrograms/kg, i.v.). CIS-19 (5 mg/kg, i.v.) did not inhibit the increase in lung resistance induced by ovalbumin (2 mg/kg, i.v.) in actively sensitized guinea-pigs. PAF (30 ng/kg, i.v.)-induced microvascular leakage, measured by the extravasation of Evans blue dye, was dose-dependently inhibited by CIS-19 (0.5-5 mg/kg, i.v.) in the trachea, main bronchi and intrapulmonary airways, but it did not affect histamine (30 micrograms/kg, i.v.)- or substance P (6.5 micrograms/kg, i.v.)-induced microvascular leakage at all airway levels. CIS-19 (2.5 and 5 mg/kg) did not affect ovalbumin (2 mg/kg, i.v.)-induced microvascular leakage in all airway levels in actively sensitized guinea-pigs, CIS-19 (2.5 and 5 mg/kg, i.v.) significantly inhibited PAF-induced enhancement of the bronchial response to methacholine, but had no effect on ovalbumin (0.05 mg/kg, i.v.)-induced bronchial hyperreactivity in actively sensitized guinea-pigs. It is concluded that CIS-19 is a potent PAF receptor antagonist which inhibits PAF- but not antigen-induced bronchoconstriction, microvascular leakage and bronchial hyperreactivity. These results suggest that PAF plays little or no role in early airway responses following antigen challenge.

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PAF and Antigen-Induced Bronchial Hyperreactivity in Guinea Pigs

Milne

Rossi

Chapman

1996

Airways Smooth Muscle: Modelling the Asthmatic Response in Vivo

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The effect of Paf antagonists on bronchial hyperresponsiveness induced by Paf, propranolol or indomethacin

Cited by 20 publications

References 26 publications

Increased airway reactivity in the guinea‐pig follows exposure to intravenous isoprenaline.

Increased airway reactivity in the guinea‐pig follows exposure to intravenous isoprenaline.

The effect of the selective PAF antagonist CIS-19 on PAF- and antigen-induced bronchoconstriction, microvascular leakage and bronchial hyperreactivity in guinea-pigs

PAF and Antigen-Induced Bronchial Hyperreactivity in Guinea Pigs

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