Contribution of a cholinergic reflex mechanism to allergen‐induced bronchial hyperreactivity in permanently instrumented, unrestrained guinea‐pigs

Santing, Ruud E.; Pasman, Yfke; Olymulder, Clemens G.; Roffel, Ad F.; Zaagsma, Johan

doi:10.1111/j.1476-5381.1995.tb13242.x

Cited by 38 publications

(31 citation statements)

References 16 publications

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“…Several studies demonstrated similarities between sensitized guinea pigs to OA and different characteristics of asthma [18][19][20][21]. McCaig [9] indicated unimpairment of ß-receptor-mediated inhibitory response elicited by sympathetic nerve stimulation.…”

Section: Discussionmentioning

confidence: 99%

Increased Tracheal Responsiveness to Beta-Adrenergic Agonist and Antagonist in Ovalbumin-Sensitized Guinea Pigs

Boskabady

Zarei²

2004

Pharmacology

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Despite the controversy of bronchial responsiveness to β₂-agonist drugs in asthma, in a previous study we have shown increased responsiveness of asthmatic tracheobronchial tree to isoprenaline. Therefore, in the present study, tracheal responsiveness to isoprenaline and also β-adrenergic receptor blockade were studied in sensitized guinea pigs. An experimental model of asthma was induced in guinea pigs by sensitization of animals with injection and inhalation of ovalbumin (OA). The responses of tracheal chains of sensitized and control animals to cumulative concentrations of isoprenaline (I) in the absence and presence of 10 nmol/l propranolol were measured, and the effective concentration of I causing 50% of maximum response (EC₅₀ I) was obtained. The propranolol blockade (CR – 1) was calculated by: (post-propranolol EC₅₀ I/EC₅₀ I) – 1. Tracheal responses of sensitized and control animals to cumulative concentrations of methacholine (M) were also measured and EC₅₀ M were obtained. The tracheal responses of sensitized guinea pig to isoprenaline was significantly higher than that of the control animals (EC₅₀ I for sensitized and control animals were 0.24 ± 0.04 and 0.58 ± 0.07 µmol/l, respectively; p < 0.001).The β-adrenergic receptor blockade by propranolol (CR – 1) was also significantly higher in sensitized guinea pigs than that of the control animals (p < 0.001). The results of this study indicate an increased tracheal response to β-adrenergic-stimulating drug and enhancement of β-adrenergic blockade by propranolol in the sensitized guinea pig.

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Section: Discussionmentioning

confidence: 99%

Increased Tracheal Responsiveness to Beta-Adrenergic Agonist and Antagonist in Ovalbumin-Sensitized Guinea Pigs

Boskabady

Zarei²

2004

Pharmacology

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“…Autoinhibitory muscarinic M 2 receptors, activated by acetylcholine itself, represent an important negative feedback, limiting further release, particularly at higher frequencies [139]. In animal models of allergic and viral airway inflammation and asthma, dysfunction of these M 2 autoreceptors has been found to contribute to exaggerated acetylcholine release from vagal nerve endings, increased cholinergic reflex activity in response to inhaled stimuli and AHR [140][141][142]. In allergic guinea pigs, the magnitude of the early asthmatic reaction has been reported to correlate significantly with the extent of M 2 autoreceptor dysfunction [142].…”

Section: Cholinergic Mechanismsmentioning

confidence: 99%

“…1). Thus AHR following the early asthmatic reaction is reversed by anticholinergics [141], and the bronchoconstrictor response of inhaled inflammatory mediators (e.g. histamine and thromboxane A 2 ) is, to a large extent, mediated by cholinergic pathways [141,159].…”

Section: Cholinergic Mechanismsmentioning

confidence: 99%

Airway hyperresponsiveness in asthma: lessons fromin vitromodel systems and animal models: Fig. 1—

Gosens¹,

Zaagsma²

2008

Eur Respir J

107

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Airway hyperresponsiveness (AHR) is a hallmark clinical symptom of asthma. At least two components of AHR have been identified: 1) baseline AHR, which is persistent and presumably caused by airway remodelling due to chronic recurrent airway inflammation; and 2) acute and variable AHR, which is associated with an episodic increase in airway inflammation due to environmental factors such as allergen exposure.Despite intensive research, the mechanisms underlying acute and chronic AHR are poorly understood. Owing to the complex variety of interactive processes that may be involved, in vitro model systems and animal models are indispensable to the unravelling of these mechanisms at the cellular and molecular level.The present paper focuses on a number of translational studies addressing the emerging central role of the airway smooth muscle cell, as a multicompetent cell involved in acute airway constriction as well as structural changes in the airways, in the pathophysiology of airway hyperresponsiveness.

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“…The animals were sensitized with 100 µg ovalbumin and 100 mg aluminum hydroxide per ml of normal saline [21]. Control group animals received the vehicle alone.…”

Section: Sensitization Of Guinea Pigsmentioning

confidence: 99%

Critical Role of Protein Kinase C (PKC) in the Onset of Airway Hypersensitivity in Ova-Sensitized Guinea Pig Model of Asthma

Mishra¹,

Kulshrestha²,

Chhabra³

et al. 2014

OJRD

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Background and Objectives: Protein kinase C (PKC) activation plays an important role in activation of T-lymphocytes in asthma.Airway hypersensitivity is one of the main characteristic features of asthma, the mechanism of onset of which is not clearly understood. Therefore, the objective was to elucidate the role of PKC in etiopathogenesis of airway hypersensitivity in asthma. Methods: Male guinea pigs (n = 30) were sensitized with ovalbumin and day of initial allergen-specific immune response determined by intradermal test, airway hypersensitivity, BALF cytology and lung histopathology. Total PKC activity, PKC isoenzymes and phosphoinositides were assessed in airway smooth muscles (ASM) and peripheral blood lymphocytes. Results: Intradermal test revealed that day 9 was the earliest time of allergen-specific response and onset of airway hypersensitivity to ovalbumin. It was associated with significant increase in total and differential (lymphocytes and eosinophils) BALF counts and grade I peribronchiolar chronic lymphocytic inflammation in lung. On day 14, grade II infiltration of lymphocytes and eosinophils with onset ofstructural remodelingofproximal and distal airways was seen. Total PKC activity, expression of PKCα, PKCε and phosphoinositides increased significantly in ASM and lymphocytes on day 9 and were maximum on day 14. There was no change in PKC-τ expression. Conclusions: Activation of PKC, particularly PKCα and PKCε, mediated signal transduction pathway plays a critical role in lymphocyte infiltration and onset of airway hypersensitivity, airway remodeling and asthma pathophysiology. The present study is the first one on the mechanism of the etiopathogenesis of the disease, which shows a direct evidence of the role of PKC mediated pathway in the initiation and onset of airway hypersensitivity in ovalbumin sensitized guinea pig model.

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Contribution of a cholinergic reflex mechanism to allergen‐induced bronchial hyperreactivity in permanently instrumented, unrestrained guinea‐pigs

Cited by 38 publications

References 16 publications

Increased Tracheal Responsiveness to Beta-Adrenergic Agonist and Antagonist in Ovalbumin-Sensitized Guinea Pigs

Increased Tracheal Responsiveness to Beta-Adrenergic Agonist and Antagonist in Ovalbumin-Sensitized Guinea Pigs

Airway hyperresponsiveness in asthma: lessons fromin vitromodel systems and animal models: Fig. 1—

Critical Role of Protein Kinase C (PKC) in the Onset of Airway Hypersensitivity in Ova-Sensitized Guinea Pig Model of Asthma

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