The Contribution of Histamine to Immediate Bronchoconstriction Provoked by Inhaled Allergen and Adenosine 5′ Monophosphate in Atopic Asthma

Rafferty, P.; Beasley, Richard; Holgate, Stephen T.

doi:10.1164/ajrccm/136.2.369

Cited by 174 publications

(86 citation statements)

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“…35 Binks et al showed that chest tightness may occur in association with bronchoconstriction, in subjects ventilated passively on a mechanical ventilator and that production of an elevated FRC with ventilator generated positive end expiratory pressure did not result in chest tightness. 36 Furthermore, Taguchi et al suggested that dyspnea sensation may result from stimulation of airway receptors when they observed a reduced sensation of dyspnea during histamine-induced bronchoconstriction under airway anesthesia by lidocaine aerosol inhalation. 37 We observed a correlation between maximum decreases in FEV1 and IC following MC, but again, breathlessness scores were not correlated with the decrease in IC.…”

Section: Discussionmentioning

confidence: 99%

Lung hyperinflation, perception of bronchoconstriction and airway hyperresponsiveness

Boulet¹,

Turcotte²

2007

CIM

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Purpose: To compare the influence of underlying airway inflammation and lung hyperinflation on dyspnea during induced bronchoconstriction in subjects with mild asthma (or asymptomatic airway hyperresponsiveness (AAHR). Methods: Fourteen mild asthmatic and 14 AAHR subjects had methacholine and 5'-adenosine monophosphate (AMP) challenges, and induced sputum analysis. Changes in inspiratory capacity (IC) and respiratory symptom scores were measured after challenges. Perception of respiratory symptoms was recorded on a modified Borg scale. Results: The mean baseline FEV1, IC, mean provocative concentration of methacholine inducing a 20% decrease in FEV1 (PC20), the mean PC20 AMP and median inflammatory cell counts were similar in both groups. After methacholine, mean (±SD) reductions in FEV1 were 24.7±10.3% in mild asthma and 35.6±19.1% in AAHR (P>0.05); reductions in IC were, respectively, 10±12% and 24±20% (P>0.05); mean breathlessness scores at PC20 were 1.1 in mild asthma and 0 in AAHR P=0.003), and mean chest tightness scores were 1.2 in mild asthma and 0.8 in AAHR (P>0.05). Maximum chest tightness scores following MC correlated with the maximum decrease in IC in mild asthma (rs=0.75,P=0.009) and with the maximum decrease in FEV1 in AAHR (rs=0.60,P=0.04). After AMP, symptom scores were not significantly correlated with decreases in FEV1 or IC. The number of inflammatory cells was not correlated with decreases in IC after methacholine, AMP or with their PC20s, although inflammation was minimal in both groups. Conclusion: Lower breathlessness scores in AAHR compared to mild asthma were not explained by differences in lung hyperinflation nor in airway inflammation.

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Section: Discussionmentioning

confidence: 99%

Lung hyperinflation, perception of bronchoconstriction and airway hyperresponsiveness

Boulet¹,

Turcotte²

2007

CIM

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“…Adenosine has been implicated to contribute to the pathophysiology of asthma as inhaled adenosine provokes bronchoconstriction in asthmatic but not normal patients (38). The response to adenosine is believed to be predominantly mediated through mast cell activation (39). Attempts to elucidate definitively the adenosine receptor subtype that mediates mast cell activation has been pharmacologically difficult due to lack of agonists and antagonists that display sufficient selectivity to discriminate between multiple adenosine receptor subtypes present on these cells.…”

Section: Discussionmentioning

confidence: 99%

Disruption of the A3 Adenosine Receptor Gene in Mice and Its Effect on Stimulated Inflammatory Cells

Salvatore¹,

Tilley²,

Latour³

et al. 2000

Journal of Biological Chemistry

283

231

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The A 3 adenosine receptor (A3AR) is one of four receptor subtypes for adenosine and is expressed in a broad spectrum of tissues. In order to study the function of A3AR, a mouse line carrying a mutant A 3 allele was generated. Mice homozygous for targeted disruption of the A3AR gene, A3AR ؊/؊ , are fertile and visually and histologically indistinguishable from wild type mice. The lack of a functional receptor in the A3AR ؊/؊ mice was confirmed by molecular and pharmacological analyses. The absence of A3AR protein expression in the A3AR ؊/؊ mice was demonstrated by lack of N 6 -(4-amino-3-[ 125 I]iodobenzyl)adenosine binding to bone marrowderived mast cell membranes that were found to express high levels of A3AR in wild type mice. In A3AR ؊/؊ mice, the density of A 1 and A 2A adenosine receptor subtypes was the same as in A3AR ؉/؉ mice as determined by radioligand binding to brain membranes. Additionally, A 2B receptor transcript expression was not affected by ablation of the A3AR gene. A3AR ؊/؊ mice have basal heart rates and arterial blood pressures indistinguishable from A3AR ؉/؉ mice. Functionally, in contrast to wild type mice, adenosine and the A3AR-specific agonist, 2-chloro-N 6 -(3-iodobenzyl)-adenosine-5-N-methylcarboxamide (2-Cl-IB-MECA), elicit no potentiation of antigen-dependent degranulation of bone marrow-derived mast cells from A3AR ؊/؊ mice as measured by hexosaminidase release. Also, the ability of 2Cl-IB-MECA to inhibit lipopolysaccharide-induced tumor necrosis factor-␣ production in vivo was decreased in A3AR ؊/؊ mice in comparison to A3AR ؉/؉ mice. The A 2A adenosine receptor agonist, 2-p-(2-carboxyethyl)phenylamino)-5-Nethylcarboxamidoadenosine, produced inhibition of lipopolysaccharide-stimulated tumor necrosis factor-␣ production in both A3AR ؊/؊ and A3AR ؉/؉ mice. These results show that the inhibition in vivo can be mediated by multiple subtypes, specifically the A 3 and A 2A adenosine receptors, and A3AR activation plays an important role in both pro-and anti-inflammatory responses.Adenosine is a naturally occurring nucleoside that exhibits diverse and potent physiological responses in the central nervous system and the cardiovascular, renal, pulmonary, and immune systems. The actions of adenosine are mediated through G-protein-coupled receptors classified into four subtypes, A 1 , A 2A , A 2B , and A 3 , on the basis of their affinity order profiles for agonists and antagonists (1-3). The A 3 adenosine receptor (A3AR) 1 is the most recent subtype identified, since it had remained pharmacologically obscure until its gene was cloned in the early 1990s. The A3AR has been cloned from multiple species including rat (4, 5), human (6, 7), sheep (8), canine (9), and rabbit (10).The physiological importance of the A 3 adenosine receptor has not been established. A3AR is expressed in a broad spectrum of tissues. The most abundant expression in human is found in lung and aorta (7). The evaluation of the functional role of the A3AR has been hampered by the presence of multiple adenosine receptor s...

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“…However, RS-601 did not affect the antigen-induced IAR in this model. Rafferty et al [29] reported that histamine participated in IAR observed in atopic asthmatic patients. In our model, histamine was markedly increased in BALF, corresponding to the appearance of IAR [30], and the IAR was clearly inhibited by the histamine H 1 receptor antagonist terfenadine [31].…”

Section: Discussionmentioning

confidence: 99%

Effects of RS-601, a Novel Leukotriene D<sub>4</sub>/Thromboxane A<sub>2</sub> Dual Receptor Antagonist, on Asthmatic Responses in Guinea Pigs

Yamada

Takahashi²,

Ishizaki³

et al. 2003

Pharmacology

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The effects of 4-[4-[5,5,6,6,6-pentafluoro-1-(4-fluorobenzene-sulfonamido)hexyl]phenyl]butyric acid (RS-601), a novel leukotriene D₄ (LTD₄)/thromboxane A₂ (TxA₂) dual receptor antagonist, on bronchial asthmatic responses in guinea pigs were examined. The effects were compared with those of pranlukast (LTD₄ receptor antagonist) and S-1452 (TxA₂ receptor antagonist). RS-601 inhibited the increase in airway resistance caused by LTD₄ and TxA₂ mimetic compound, U-46619, but not by histamine. RS-601 and pranlukast but not S-1452 inhibited an antigen-induced late asthmatic response. In addition, RS-601 inhibited an antigen-induced airway hyperresponsiveness (AHR), whereas pranlukast and S-1452 had no effect on the AHR. The antigen-induced increase in inflammatory cells in airway was not affected by all examined agents. Furthermore, bacterial lipopolysaccharide-induced AHR in guinea pigs was clearly suppressed by RS-601 but not by pranlukast and S-1452. The increase in airway inflammatory cells caused by lipopolysaccharide was not affected by all three drugs. These findings indicate that RS-601 has a potent antiasthmatic efficacy, especially on AHR, but does not affect accumulation of eosinophils in the airways.

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The Contribution of Histamine to Immediate Bronchoconstriction Provoked by Inhaled Allergen and Adenosine 5′ Monophosphate in Atopic Asthma

Cited by 174 publications

References 7 publications

Lung hyperinflation, perception of bronchoconstriction and airway hyperresponsiveness

Lung hyperinflation, perception of bronchoconstriction and airway hyperresponsiveness

Disruption of the A3 Adenosine Receptor Gene in Mice and Its Effect on Stimulated Inflammatory Cells

Effects of RS-601, a Novel Leukotriene D<sub>4</sub>/Thromboxane A<sub>2</sub> Dual Receptor Antagonist, on Asthmatic Responses in Guinea Pigs

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