The Rabbit Model of Asthma and the Late Asthmatic Response

Herd, Caroline M.; Page, Clive

doi:10.1007/978-3-0348-9000-7_7

Cited by 3 publications

(3 citation statements)

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“…Both allergic rabbits and allergic humans share many common features of asthma. These features include airway hyperreactivity to adenosine, histamine, acetylcholine, platelet-activating factor, development of inflammation and permeability changes in the airways, release of mediators, including neutrophil and eosinophil chemotactic factors, production of antigen-specific IgE antibodies, and mast cell dependence (Larsen et al, 1984;Metzger et al, 1989;Herd and Page, 1996;Gozzard et al, 1997;Gascoigne et al, 2003). Moreover, adenosine levels are increased in the bronchoalveolar fluid of both humans and rabbits with allergic asthma (Ali et al, 1992b;Driver et al, 1993).…”

Section: Discussionmentioning

confidence: 99%

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A Novel A1 Adenosine Receptor Antagonist, L-97-1 [3-[2-(4-Aminophenyl)-ethyl]-8-benzyl-7-{2-ethyl-(2-hydroxy-ethyl)-amino]-ethyl}-1-propyl-3,7-dihydro-purine-2,6-dione], Reduces Allergic Responses to House Dust Mite in an Allergic Rabbit Model of Asthma

Obiefuna¹,

Batra²,

Nadeem³

et al. 2005

The Journal of Pharmacology and Experimental Therapeutics

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Adenosine, an important signaling molecule in asthma, produces bronchoconstriction in asthmatics. Adenosine produces bronchoconstriction in allergic rabbits, primates, and humans by activating A 1 adenosine receptors (ARs). Effects of L-97-1 [3-[2-(4-aminophenyl)-ethyl]-8-benzyl-7-{2-ethyl-(2-hydroxyethyl)-amino]-ethyl}-1-propyl-3,7-dihydro-purine-2,6-dione] a water-soluble, small molecule A 1 AR antagonist were investigated on early and late phase allergic responses (EAR and LAR) in a hyper-responsive rabbit model of asthma. Rabbits were made allergic by intraperitoneal injections of house dust mite [HDM; 312 allergen units (AU)] extract within 24 h of their birth. Booster HDM injections were given weekly for 1 month, biweekly for 4 months, and continued monthly thereafter. Hyperresponsiveness was monitored by measuring lung dynamic compliance (Cdyn), after histamine or adenosine aerosol challenge in allergic rabbits. Hyper-responsive rabbits were subjected to aerosol of HDM (2500 AU), 1 h after intragastric administration of L-97-1 (10 mg/kg) solution or an equivalent volume of saline. Cdyn was significantly higher after treatment with L-97-1 compared with untreated controls (p Ͻ 0.05 n ϭ 5). Histamine PC 30 was significantly higher (p Ͻ 0.05; n ϭ 5) after L-97-1 at 24 h compared with histamine PC 30 at 24 h after HDM. Adenosine PC 30 was significantly higher at 15 min and 6 h after L-97-1 compared with control (p Ͻ 0.05; n ϭ 5). L-97-1 showed strong affinity for human A 1 ARs in radioligand binding studies and no inhibition toward human phosphodiesterase II, III, IV, and V enzymes. These data suggest that L-97-1 produces a significant reduction of histamine or adenosineinduced hyper-responsiveness and HDM-induced EAR and LAR in allergic rabbits by blocking A1 ARs and may be beneficial as an oral therapy for human asthma.Adenosine is an endogenous nucleoside-signaling molecule and acts on adenosine receptors (ARs) to produce a number of physiological effects in humans, including bronchoconstriction and lung inflammation. Moreover, it is becoming increasingly apparent that adenosine is an important signaling molecule in human asthma. When administered by inhalation, adenosine produces concentration-dependent bronchoconstriction in patients with asthma, but not in normal subjects (Cushley et al., 1983;Polosa, 2002;Rorke and Holgate, 2002). Adenosine levels are increased in the bronchoalveolar fluid of asthmatics and also in the plasma of patients with exercise-induced asthma (Driver et al., 1993;Vizi et al., 2002). There is also an association between allergen exposure and adenosine monophosphate (AMP) responsiveness in asthmatics (Currie et al., 2003). In asthma, the airway re-

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Section: Discussionmentioning

confidence: 99%

“…Previously, it was reported that the allergic rabbit model simulates the human condition of asthma (Metzger et al, 1989;Herd and Page, 1996). Both allergic rabbits and allergic humans behave similarly to airway hyperreactivity to adenosine, histamine, acetylcholine, and platelet-activating factor.…”

mentioning

confidence: 99%

A Novel A1 Adenosine Receptor Antagonist, L-97-1 [3-[2-(4-Aminophenyl)-ethyl]-8-benzyl-7-{2-ethyl-(2-hydroxy-ethyl)-amino]-ethyl}-1-propyl-3,7-dihydro-purine-2,6-dione], Reduces Allergic Responses to House Dust Mite in an Allergic Rabbit Model of Asthma

Obiefuna¹,

Batra²,

Nadeem³

et al. 2005

The Journal of Pharmacology and Experimental Therapeutics

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“…Given the similarities between this allergic rabbit model and the responses to inhaled substances seen in human asthma ( Herd & Page, 1996 ), we have utilized the model to investigate, firstly, whether GCS can reverse baseline AHR, once it has been established, and, secondly, whether treatment with GCS from birth can prevent the development of baseline AHR.…”

Section: Introductionmentioning

confidence: 99%

Effects of dexamethasone on airway hyper‐responsiveness to the adenosine A₁ receptor agonist cyclo‐pentyl adenosine in an allergic rabbit model

El-Hashim

Banner

Paul

et al. 1999

British J Pharmacology

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New Zealand White (NZW) rabbits were immunized within 24 h of birth with Alternaria tenuis in aluminium hydroxide (Al (OH)3) (i.p.) or sham immunized (saline plus Al (OH)3 i.p.) and subsequently injected with the allergen (i.p.) or sham‐immunized for the next 3 months. At 3 months of age, baseline airway responsiveness was assessed using cyclo‐pentyl adenosine (CPA). Bronchoalveolar lavage (BAL) was performed in all animals and samples of peripheral blood were collected from some animals for estimation of dexamethasone levels. In some animals, blood was collected at the end of the experiment and cellular function was assessed by measurement of ex vivo proliferation of mononuclear cells in response to phytohaemagglutinin (PHA). Allergen immunization significantly increased baseline airway responsiveness to inhaled CPA (P<0.05) in comparison with sham‐immunized animals, at 3 months after immunization. Dexamethasone (0.5 mg kg−1 day−1) treatment for 1 month did not modify this established airway hyper‐responsiveness to CPA. Dexamethasone treatment did not affect either total or differential cell numbers in BAL fluid during the 4 week period, although significant plasma levels of dexamethasone were achieved in dexamethasone treated animals. Treatment of rabbits with dexamethasone (0.1 mg kg−1 i.p.), 6 h prior to each allergen injection from the neonatal stage, significantly reduced baseline airway hyper‐responsiveness to CPA measured at 3 months (P<0.05). There was no significant difference in either total or differential cell numbers in BAL fluid, or any difference in mitogen‐induced proliferation of mononuclear cells between dexamethasone and vehicle treated rabbits. These results suggest that introduction of glucocorticosteroids in early life can prevent baseline airway hyper‐responsiveness to inhaled CPA in allergic rabbits. However, once established, such underlying airway hyper‐responsiveness is difficult to resolve, even with prolonged treatment with glucocorticosteroids. British Journal of Pharmacology (1999) 126, 1513–1521; doi:

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Novel Anti-inflammatory Therapies

Barnes

Page

2004

Handbook of Experimental Pharmacology

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The Rabbit Model of Asthma and the Late Asthmatic Response

Cited by 3 publications

References 92 publications

A Novel A1 Adenosine Receptor Antagonist, L-97-1 [3-[2-(4-Aminophenyl)-ethyl]-8-benzyl-7-{2-ethyl-(2-hydroxy-ethyl)-amino]-ethyl}-1-propyl-3,7-dihydro-purine-2,6-dione], Reduces Allergic Responses to House Dust Mite in an Allergic Rabbit Model of Asthma

A Novel A1 Adenosine Receptor Antagonist, L-97-1 [3-[2-(4-Aminophenyl)-ethyl]-8-benzyl-7-{2-ethyl-(2-hydroxy-ethyl)-amino]-ethyl}-1-propyl-3,7-dihydro-purine-2,6-dione], Reduces Allergic Responses to House Dust Mite in an Allergic Rabbit Model of Asthma

Effects of dexamethasone on airway hyper‐responsiveness to the adenosine A₁ receptor agonist cyclo‐pentyl adenosine in an allergic rabbit model

Novel Anti-inflammatory Therapies

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The Rabbit Model of Asthma and the Late Asthmatic Response

Cited by 3 publications

References 92 publications

A Novel A1 Adenosine Receptor Antagonist, L-97-1 [3-[2-(4-Aminophenyl)-ethyl]-8-benzyl-7-{2-ethyl-(2-hydroxy-ethyl)-amino]-ethyl}-1-propyl-3,7-dihydro-purine-2,6-dione], Reduces Allergic Responses to House Dust Mite in an Allergic Rabbit Model of Asthma

A Novel A1 Adenosine Receptor Antagonist, L-97-1 [3-[2-(4-Aminophenyl)-ethyl]-8-benzyl-7-{2-ethyl-(2-hydroxy-ethyl)-amino]-ethyl}-1-propyl-3,7-dihydro-purine-2,6-dione], Reduces Allergic Responses to House Dust Mite in an Allergic Rabbit Model of Asthma

Effects of dexamethasone on airway hyper‐responsiveness to the adenosine A1 receptor agonist cyclo‐pentyl adenosine in an allergic rabbit model

Novel Anti-inflammatory Therapies

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Product

Resources

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Effects of dexamethasone on airway hyper‐responsiveness to the adenosine A₁ receptor agonist cyclo‐pentyl adenosine in an allergic rabbit model