Pharmacological Differentiation of Allergic and Classically Conditioned Asthma in the Guinea Pig

Justesen, Don R.; Braun, Edward W.; Garrison, Robert G.; Pendleton, Robert B.

doi:10.1126/science.170.3960.864

Cited by 40 publications

(16 citation statements)

References 8 publications

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“…8) These findings thus indicated that bronchoconstriction play a role in rat IAR but not in rat LAR, consistent with the findings of a previous study in guinea pig. 4,6) On the other hand, LT is involved in rat IAR but not in rat LAR. In clinical studies of asthma, anti-LTs reduced antigen-induced LAR by only about 50%, 23,24) suggesting that other mechanisms not related to LT are involved in LAR.…”

Section: Discussionmentioning

confidence: 99%

“…For example, it is known that antileukotrienes reduce LAR in guinea pig, while antihistamines do not. 4,5) On the other hand, inhalation of a b 2 -agonist like salbutamol, which directly inhibits the contraction of airway smooth muscle, diminishes IAR but not LAR. 6) Further, anti-IL-5 monoclonal antibody decrease infiltration of eosinophils into the tracheal wall, and also markedly suppresses the development of LAR in guinea pig.…”

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confidence: 99%

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Pharmacological Analysis of Antigen-Induced Late Airway Response in Rats

Miyagawa

Iwasaki

Kato

et al. 2009

Biological & Pharmaceutical Bulletin

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Bronchial asthma is one of the most common allergic diseases in the world, and is considered a complex inflammatory disorder of the airways with various pathophysiological features.1) The exposure of asthmatics to specific antigens causes airway symptoms which can be generally distinguished into two predominant airway reactions, an immediate airway response (IAR) and a late airway response (LAR). 2,3)The pharmacological profiles of antigen-induced IAR and LAR have been determined using animal models, especially in the guinea pig. For example, it is known that antileukotrienes reduce LAR in guinea pig, while antihistamines do not. 4,5) On the other hand, inhalation of a b 2 -agonist like salbutamol, which directly inhibits the contraction of airway smooth muscle, diminishes IAR but not LAR.6) Further, anti-IL-5 monoclonal antibody decrease infiltration of eosinophils into the tracheal wall, and also markedly suppresses the development of LAR in guinea pig. 7)In recent years, the pharmaceutical targets for new asthmatic drugs have become more immunologically diverse and specific, and detailed immunological analysis of mechanisms in animal models is required to determine with precision the efficacies of new drug candidates. However, the guinea pig model is not sufficient for this purpose, since immunological and genetic research on guinea pigs has not been performed in detail.In this regard, we have examined the pharmacological and immunological characteristics of ovalbumin (OVA)-induced IAR and LAR in the rat. Briefly, rat IAR exhibits diverse immunological characteristics, i.e. a quick phase (3-6 min after challenge) caused by the exocytosis of mediators in CTMCs and an early phase (6-30 min after challenge) mediated by leukotriene (LT) and TXA 2 .8) In addition, repeated antigen inhalation by sensitized rats converts IAR to LAR, a reaction triggered by antigen-specific immunoglobulin G (IgG). 9)In the present study, the pharmacological profiles of rat LAR were examined using rat LAR model. To clarify the pharmacological profile of rat LAR, the effects of antiasthmatic drugs including salbutamol (b 2 -agonist), ketotifen (antihistamine), pranlukast (anti-leukotriene C 4 /D 4 /E 4 ), and prednisolone (steroid) were evaluated. In addition, the involvement of cell infiltration in bronchoalveolar lavage fluid (BALF) and pulmonary edema in LAR were investigated in the rat model. MATERIALS AND METHODS AnimalsMale Sprague-Dawley (SD) rats were purchased from Charles River Japan, Inc. (CRJ, Yokohama, Japan) and individually housed in plastic cages maintained under specific pathogen-free conditions at a room temperature of 23.0Ϯ3.0°C and air humidity of 55Ϯ15% in a 12-h light/dark cycle environment. The rats were given a standard laboratory chow diet (CRF-1, Oriental Yeast, Tokyo, Japan) and water ad libitum. All experiments complied with the Guidelines for Animal Experimentation of our laboratories.Compounds The antihistamine ketotifen (Sigma-Aldrich Co.); anti-LT (leukotriene C 4 /D 4 /E 4 receptor antagonist) pranlukas...

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Pharmacological Analysis of Antigen-Induced Late Airway Response in Rats

Miyagawa

Iwasaki

Kato

et al. 2009

Biological & Pharmaceutical Bulletin

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“…22) The guinea pig asthmatic model exhibits two phases, IAR over a few minutes and LAR during a few hours after antigen exposure. 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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“…Subsequent exposure to previously ineffective concentrations, or to other stimuli associated with chemical irritation, might result in the elicitation of conditioned responses that are unpleasant in and of themselves or have behavioral or other effects" (13 (25). MacQueen et al (26) demonstrated that a protease specific to mast cells was released in response to an audiovisual CS that had in the past been paired with EA in rats sensitized to the protein.…”

Section: Sensitization To Irritants As a Learned Responsementioning

confidence: 99%

Pavlovian Conditioning and Multiple Chemical Sensitivity

Siegel¹,

Kreutzer²

1997

Environmental Health Perspectives

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Pavlovian conditioning processes may contribute to some symptoms of multiple chemical sensitivity (MCS). This review summarizes the potential relevance of the literature on conditional taste and olfactory aversions, conditional sensitization, and conditional immunomodulation to understanding MCS. A conditioning-based perspective on MCS suggests novel research and treatment strategies. -Environ Health Perspect 1 05(Suppl 2): 521-526 (1997)

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Pharmacological Differentiation of Allergic and Classically Conditioned Asthma in the Guinea Pig

Cited by 40 publications

References 8 publications

Pharmacological Analysis of Antigen-Induced Late Airway Response in Rats

Pharmacological Analysis of Antigen-Induced Late Airway Response in Rats

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

Pavlovian Conditioning and Multiple Chemical Sensitivity

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