Pathogenesis of Asthma: A Review

Barnes, Peter J.

doi:10.1177/014107688307600711

Cited by 14 publications

(8 citation statements)

References 60 publications

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“…Furthermore, it has been suggested (Barnes et al, 1988) that epithelium cell loss might provoke bronchial hyperreactivity by making sensory nerve terminals more accessible to inhaled noxious stimuli. If this hypothesis is correct, it implies that bronchial hyperreactivity in asthma must (at least in part) have an underlying neurogenic basis.…”

Section: Discussionmentioning

confidence: 99%

The effects of epithelium removal on the actions of cholinomimetic drugs in opened segments and perfused tubular preparations of guinea‐pig trachea

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Dixon

et al. 1990

British J Pharmacology

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Isolated segments of guinea‐pig trachea or perfused tracheal tubes were arranged for the recording of trachealis tension changes in Krebs solution containing indomethacin (2.8 μm). In opened tracheal segments, epithelium removal caused modest (2–3 fold) potentiation of the effects of acetylcholine (ACh) and methacholine (MeCh) but failed to potentiate carbachol (CCh), bethanechol (BeCh), oxotremorine or KCl. Pretreatment with ecothiopate potentiated effects of ACh and MeCh but not of CCh or BeCh. Removal of epithelium in ecothiopate‐treated tissue potentiated effects of ACh and MeCh but not of CCh or BeCh. Guinea‐pig ileum challenged with ACh was used as a bioassay system for cholinesterase activity. Scrapings of tracheal epithelium did not hydrolyse ACh. Histochemical staining revealed no fibres positive for acetylcholinesterase or pseudocholinesterase in the tracheal epithelium. However, the underlying tissues contained acetylcholinesterase‐positive nerve fibres and the trachealis muscle itself stained positively for pseudocholinesterase activity. Neither tetrodotoxin (3 μm) nor hexamethonium (500 μm) modified the ability of epithelium removal to potentiate ACh. In perfused tracheal tubes where spasmogens were added to the luminal perfusate, epithelium removal potentiated effects of ACh (31 fold), CCh (10 fold), oxotremorine (2 fold) and KCl. In perfused tracheal tubes where spasmogens were added to the Krebs solution superfusing the adventitial surface of the tissue, epithelium removal significantly reduced the potency of CCh, oxotremorine and KCl. It is concluded that the selectivity and magnitude of the potentiation of cholinomimetics caused by epithelium removal depends on the route by which the cholinomimetic agent gains access to the trachealis muscle. The potentiation of acetic acid esters of choline seen in opened tracheal segments does not reflect the loss of epithelial cholinesterase activity and does not depend on the activity of nervous reflex arcs in the tracheal wall. The reduced potency of adventitially‐applied cholinomimetics and KCl seen in epithelium‐denuded tissue strongly suggests that the epithelium can moderate trachealis sensitivity to cholinomimetic agents not only by releasing epithelium‐derived relaxing factor but also by acting as a barrier to drug diffusion.

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Section: Discussionmentioning

confidence: 99%

The effects of epithelium removal on the actions of cholinomimetic drugs in opened segments and perfused tubular preparations of guinea‐pig trachea

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Good

Dixon

et al. 1990

British J Pharmacology

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“…Airway obstruction in asthma involves not only contraction of airway smooth muscle (which may involve vagal neural reflexes), but also plugging of the airways with viscous mucus, airway mucosal oedema produced by bronchial microvascular leakiness, and by inflammatory cell infiltration of the airway wall (Barnes, 1983a). Since contraction of airway smooth muslle, secretion of mucus and inflammatory mediators, neurotransmission and chemotaxis all depend on the movement of calcium ions into cells, this has prompted the suggestion that drugs which block calcium ion influx (calcium antagonists) might be beneficial in the treatment of asthma.…”

Section: Introductionmentioning

confidence: 99%

Clinical studies with calcium antagonists in asthma.

Barnes¹

1985

Brit J Clinical Pharma

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“…When neurogenic inflammation occurs in pathophysiological status such as asthma, CGRP may be released and enhance some reactions, including vasodilatation and bronchoconstriction. These reactions may lead to a deterioration in the patient's condition (Barnes et al, 1992). It is speculated that the effects of CGRP are potentiated in airways in conditions of inflammation, since the induction of ET-1 and NOS in airway epithelium have been observed in asthmatics (Vittoli et al, 1992;Hamid et al, 1993).…”

Section: Discussionmentioning

confidence: 99%

The effects of calcitonin gene‐related peptide on tracheal smooth muscle of guinea‐pigs in vitro

Ninomiya

Uchida

Endo

et al. 1996

British J Pharmacology

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1 The effect of calcitonin gene-related peptide (CGRP) on airway smooth muscle is controversial. The aim of this study was to determine whether the action of CGRP on tracheal strips of guinea-pigs is modulated by epithelium and whether this peptide-induced action involves other mediators including nitric oxide (NO) and endothelin (ET)-1.2 CGRP produced a weak dose-dependent increase in guinea-pig tracheal tension in vitro (-logEC50 = 8.5 ± 0.1, maximum contraction = 8.3 + 1.2% of 50 mM KCl-induced contraction, n = 6). In epitheliumdepleted preparations, CGRP (10'-M)-induced contraction was significantly potentiated from 9.0+1.9% to 41.1+6.0% (n=6).3 L-NG-nitro-arginine methyl ester (L-NAME, 10-4 M), which inhibits NO synthesis, enhanced the contractile response to CGRP from 9.0+1.9% to 31.2+1.1% (n=6). Indomethacin (10-5M) also enhanced the response to CGRP, although the effect was weak (13.4+3.2%, n=6). 4 Anti-ET-1 serum changed the CGRP-induced contraction into a relaxation. After incubation of the trachea with ET-1 (10-' M) to attenuate ET-1-induced responses, the CGRP-induced contraction also changed into a relaxation. BQ-123 (an ETA receptor antagonist) and BQ-788 (an ETB receptor antagonist) caused the same conversion of the CGRP response, from contraction to relaxation, although the relaxing effect elicited by BQ-788 was more potent than that by BQ-123. Maximum inhibitory responses were -31.0 + 3.3% and -13.0 + 2.3% of 50 mM KCl-induced contraction, respectively (n = 6). 5 In primary culture, guinea-pig tracheal epithelial cells released ET-1, and CGRP (10-5 M) significantly increased the release of ET-1. 6 These data suggest that the action of CGRP is modulated by airway epithelium and this mechanism involves the release of NO and ET-1. Especially, the majority of contractile action elicited by CGRP consists of an action of ET-1 via the predominant ETB receptor.

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Pathogenesis of Asthma: A Review

Cited by 14 publications

References 60 publications

The effects of epithelium removal on the actions of cholinomimetic drugs in opened segments and perfused tubular preparations of guinea‐pig trachea

The effects of epithelium removal on the actions of cholinomimetic drugs in opened segments and perfused tubular preparations of guinea‐pig trachea

Clinical studies with calcium antagonists in asthma.

The effects of calcitonin gene‐related peptide on tracheal smooth muscle of guinea‐pigs in vitro

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