Endothelins

Hay, Douglas W. P.

doi:10.1007/978-3-0348-7362-8_1

Cited by 4 publications

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“…In 1995, Peters and colleagues (47) suggested that the continuous activation of the intracellular signal transduction caused by the ␤ 2 -adrenoceptor stimulation could induce a proinflammatory process mediated by nuclear transcription factors in rat lung. A recent study in our institution showed that the transcription factor nuclear factor-B (NF-B) is involved in fenoterol-induced hyperresponsiveness to NKA in guinea pig isolated trachea (52).Endothelin-1 (ET-1) is a 21-amino acid peptide recently implicated in chronic inflammatory airway diseases such as asthma and chronic obstructive pulmonary disease (25,26,41,46). ET-1 is synthesized and metabolized in lung, and ET-1 receptors (ET A and ET B ) are widely distributed in airway cells (21,26,41).…”

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“…Endothelin-1 (ET-1) is a 21-amino acid peptide recently implicated in chronic inflammatory airway diseases such as asthma and chronic obstructive pulmonary disease (25,26,41,46). ET-1 is synthesized and metabolized in lung, and ET-1 receptors (ET A and ET B ) are widely distributed in airway cells (21,26,41).…”

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“…ET-1 is synthesized and metabolized in lung, and ET-1 receptors (ET A and ET B ) are widely distributed in airway cells (21,26,41). ET-1 is one of the most potent contractile agents of human airway smooth muscle and can induce airway inflammation, airway hyperresponsiveness, and airway remodeling in animals and humans (25,26,27,41), suggesting that ET-1 could be a major component of asthma pathophysiology (10,22,26,27). The purpose of this study was to determine the sensitizing effect of fenoterol on the contraction to ET-1 of human bronchi and to investigate the role of inflammatory mediators and signal transduction pathways involved in airway sensitization to ET-1 induced by ␤ 2 -adrenoceptor agonists.…”

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In vitro sensitization of human bronchus by β₂-adrenergic agonists

Faisy¹,

Naline²,

Diehl

et al. 2002

American Journal of Physiology-Lung Cellular and Molecular Phys

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Ϫ7 M fenoterol induced sensitization characterized by an increase in maximal contraction to endothelin-1 (ET-1) and acetylcholine (ACh). Incubation of human bronchi with 10 Ϫ6 , 3 ϫ 10 Ϫ6 , and 10 Ϫ5 M forskolin (an adenyl cyclase activator) reproduced sensitization to ET-1 and ACh. The sensitizing effect of fenoterol was inhibited by coincubation with gliotoxine (a nuclear factor-B inhibitor), dexamethasone, indomethacin (a cyclooxygenase inhibitor), GR-32191 (a TP prostanoid receptor antagonist), MK-476 (a cysteinyl leukotriene type 1 receptor antagonist), SR-140333 ϩ SR-48968 ϩ SR-142801 (neurokinin types 1, 2, and 3 tachykinin receptor antagonists) with or without HOE-140 (a bradykinin B 2 receptor antagonist), SB-203580 (an inhibitor of the 38-kDa mitogen-activated protein kinase, p38 MAPK ), or calphostin C (a protein kinase C blocker). Our results suggest that chronic exposure to fenoterol induces proinflammatory effects mediated by nuclear factor-B and pathways involving leukotrienes, prostanoids, bradykinin, tachykinins, protein kinase C, and p38 MAPK , leading to the regulation of smooth muscle contraction to ET-1 and ACh.␤ 2-agonists; airway sensitization; airway smooth muscle; endothelin-1; asthma THE FATAL ACUTE ASTHMA CASES attributable to fenoterol abuse in the 1980s in New Zealand started a controversy concerning the potential worsening of the bronchial hyperresponsiveness by the ␤ 2 -adrenoceptor agonists (7,14,42). Studies in animals and humans showed that chronic exposure to fenoterol or salbutamol induces a nonspecific bronchial sensitization, whereas the relaxant effects of these ␤ 2 -agonists on the airway smooth muscle are not decreased (11,59,60). The bronchial sensitization induced by fenoterol is similar to the sensitization provoked by ovalbumin in sensitized guinea pigs (60). Chronic administration of salbutamol at low doses to guinea pigs increases airway reactivity to histamine and methacholine (11). In humans, long-term use of salbutamol increases the bronchial hyperresponsiveness to histamine but does not cause subsensitization of ␤ 2 -adrenoceptors to salbutamol (59). In a bovine tracheal model, Katsunuma and colleagues (36) showed that prolonged incubation with fenoterol induced an increased contractile responsiveness to neurokinin A (NKA). In 1995, Peters and colleagues (47) suggested that the continuous activation of the intracellular signal transduction caused by the ␤ 2 -adrenoceptor stimulation could induce a proinflammatory process mediated by nuclear transcription factors in rat lung. A recent study in our institution showed that the transcription factor nuclear factor-B (NF-B) is involved in fenoterol-induced hyperresponsiveness to NKA in guinea pig isolated trachea (52).Endothelin-1 (ET-1) is a 21-amino acid peptide recently implicated in chronic inflammatory airway diseases such as asthma and chronic obstructive pulmonary disease (25,26,41,46). ET-1 is synthesized and metabolized in lung, and ET-1 receptors (ET A and ET B ) are widely distributed in airway cells (21,26...

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In vitro sensitization of human bronchus by β₂-adrenergic agonists

Faisy¹,

Naline²,

Diehl

et al. 2002

American Journal of Physiology-Lung Cellular and Molecular Phys

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“…The biological actions of ET‐1 are mediated through two distinct receptor subtypes, both of which belong to the G‐protein coupled receptor superfamily, termed ET A and ET B receptors ( Sakurai et al ., 1992 ; Arai et al ., 1993 ). Numerous studies have revealed the diverse biological action of this peptide in the lungs ( Hay, 1995 ; Fernandes et al ., 1996 ; Goldie et al ., 1996 ). Furthermore, immunoreactive levels of ET were found to be elevated in bronchoalveolar lavage fluid (BAL) ( Redington et al ., 1995 ) and in airway epithelium of asthmatic patients ( Springall et al ., 1991 ) compared to healthy subjects, suggesting a pathophysiological role of ET‐1 in bronchial asthma.…”

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Modulation of ET‐1‐induced contraction of human bronchi by airway epithelium‐dependent nitric oxide release via ET_A receptor activation

Naline¹,

Bertrand²,

Biyah³

et al. 1999

British J Pharmacology

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1 The purpose of this work was to investigate whether endothelin-1 (ET-1) was able to induce the release of an inhibitory factor from the airway epithelium in isolated human bronchi and to identify this mediator as well as the endothelin receptor involved in this phenomenon. 2 In intact bronchi, ET-1 induced a concentration-dependent contraction (7logEC 50 =7.92+0.09, n=18) which was potentiated by epithelium removal (7logEC 50 =8.65+0.11, n=17). BQ-123 , an ET A receptor antagonist, induced a signi®cant leftward shift of the ET-1 concentration-response curve (CRC). This leftward shift was abolished after epithelium removal. 3 L-NAME (3610 73 M), an inhibitor of nitric oxide (NO) synthase, induced a signi®cant leftward shift of the ET-1 CRC, and abolished the potentiation by BQ-123 (10 78 M) of ET-1-induced contraction. 4 In intact preparations, the ET B receptor antagonist BQ-788 induced only at 10 75 M a slight rightward shift of the ET-1 CRC. In contrast, in epithelium-denuded bronchi or in intact preparations in the presence of L-NAME, BQ-788 displayed a non-competitive antagonism toward ET-1-induced contraction. 5 IRL 1620, a selective ET B receptor agonist, induced a contraction of the isolated bronchus (7logEC 50 =7.94+0.11, n=19). This e ect was not modi®ed by epithelium removal or by BQ-123. BQ-788 exerted a competitive antagonism against IRL 1620 which was similar in the presence or absence of epithelium. 6 These results show that ET-1 exerts two opposite e ects on the human airway smooth muscle. One is contractile via ET B -receptor activation, the other is inhibitory and responsible of NO release which counteracts via ET A -receptor activation the contraction.

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