Endothelin-1 Stimulates Eicosanoid Production in Cultured Human Nasal Mucosa

Wu, Tong; Mullol, Joaquim; Rieves, R. D.; Logun, Carolea; Hausfield, Jeffrey; Kaliner, Michael; Shelhamer, James H.

doi:10.1165/ajrcmb/6.2.168

Cited by 40 publications

(24 citation statements)

References 41 publications

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“…Furthermore, ET-I (0.1 LM-10 ylM) stimulated the release of the cyclo-oxygenase products PGD2, PGE2 and TxB2 and also 15-HETE, but not 6-keto PGFI,, or the peptidoleukotrienes, from human cultured nasal mucosa (Wu et al, 1992). It is noteworthy that the greatest effect was on the release of PGD2 and it was also observed that the ET-i-induced release of eicosanoids was not affected by a PAF receptor antagonist (Wu et al, 1992).…”

Section: Discussionmentioning

confidence: 90%

Relative contributions of direct and indirect mechanisms mediating endothelin‐induced contraction of guinea‐pig trachea

Hay

Hubbard

Undem

1993

British J Pharmacology

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1 The present study was undertaken to determine the mechanism of action of endothelin-l (ET-l)-induced contraction of the guinea-pig isolated trachea.2 ET-1 (1 nM-0.3 piM) produces a concentration-dependent contraction of guinea-pig trachea with an EC50 of approximately 25 nM. The combination of the peptidoleukotriene receptor antagonist, SK&F 104353 (10 JM) and the HI-histamine receptor antagonist, mepyramine (10 pM), which abolishes antigeninduced contraction in guinea-pig trachea, was without effect on ET-1 concentration-response curves.Furthermore, the platelet-activating factor (PAF) receptor antagonist, WEB 2086, (1 or 1O pM) did not inhibit ET-induced contraction. 3 ET-l (0.3 jiM) did not stimulate histamine or immunoreactive peptidoleukotriene release from guinea-pig isolated trachea. 4 The release of various prostanoids from guinea-pig trachea was increased significantly by ET-1 (0.3 jiM); the profile of release was prostaglandin D2 (PGD2) = PGE2 = 6-keto PGFi,, (PGI2 metabolite)> thromboxane B2 = PGFk >> 9a, 111, PGF2 (PGD2 metabolite). ET-1-induced release of prostaglandins, which was about 30% of that elicited by antigen in sensitized tissues, was not affected by epithelium removal and was observed in tissues from which the smooth muscle had been removed. Previous studies in our laboratory indicated that indomethacin potentiated contraction produced by high concentrations of ET-1, whereas a thromboxane receptor antagonist was without appreciable effect on ET-l concentration-response curves.5 Pretreatment of tissues for 1 h with capsaicin (1O jiM), which depletes different sensory neurones, produced a small, but significant, inhibitory effect on ET-1 concentration-response curves in the presence but not the absence of the epithelium. The combination of the NK, tachykinin receptor antagonist, CP-96,345 (0.1 pM), and the NK2 tachykinin receptor antagonist, SR 48968 (0.1 jiM), was without effect on ET-l concentration-response curves but substantially antagonized capsaicin-induced contraction. 6 The present data suggest that in guinea-pig isolated trachea, ET-1 produces contraction predominantly via a direct mechanism: there is no significant contribution of the release of histamine, leukotrienes, PAF, or tachykinins (acting on NK, or NK2 receptors). Although ET-1 evokes the release of an array of prostanoids from the trachea they do not appear to have a major influence on the contractile response.

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Section: Discussionmentioning

confidence: 90%

Relative contributions of direct and indirect mechanisms mediating endothelin‐induced contraction of guinea‐pig trachea

Hay

Hubbard

Undem

1993

British J Pharmacology

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“…Clinical and experimental studies [3][4][5] have suggested the importance of this polypeptide in allergic airway inflammation. This polypeptide induces bronchoepithelial cells to release lipoxygenase products [26] and inhibits the proliferation of rat airway epithelial cells [27]. Therefore, ET-1 is one of the modulators of epithelial functions.…”

Section: Discussionmentioning

confidence: 99%

Erythromycin and clarithromycin attenuate cytokine-induced endothelin-1 expression in human bronchial epithelial cells

et al. 1998

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Erythromycin and its fourteen-member macrolide analogues have attracted attention for their efficacy in bronchial asthma. However, their mechanisms of action remain unclear. We evaluated the effects of the macrolide antibiotics on endothelin-1 (ET-1) expression in normal and transformed human bronchial epithelial cells, one of the sources of this potent bronchoconstrictor important in the pathogenesis of asthma. Human bronchial epithelial cells were obtained from the resected bronchi, and the effect of several antimicrobial and antiasthmatic drugs on the production and messenger ribonucleic acid (mRNA) levels of ET-1 was evaluated. Bronchoepithelial cells were also isolated from the mucosa of asthmatic patients under fibreoptic bronchoscopy, and the modulating effects of the drugs were studied. Erythromycin and clarithromycin uniquely suppressed mRNA levels as well as the release of ET- at therapeutic and non-cytotoxic concentrations (percentage inhibition of ET-1 protein release: 26.4+/-5.22% and 31.2+/-7.45%, respectively, at 10(-6) M). Furthermore, erythromycin and clarithromycin inhibited ET-1 expression in bronchoepithelial cells from patients with chronic, stable asthma. A glucocorticosteroid, dexamethasone, also inhibited ET-1 expression. In contrast, theophylline, salbutamol and FK506 had no effect on ET-1 production. Our findings demonstrated that these fourteen-member macrolide antibiotics had an inhibitory effect on endothelin-1 expression in human bronchial epithelial cells. Moreover, this new mode of action may have some relevance to their clinical efficacy in bronchial asthma.

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“…As ET-1 may be an endogenous regulator of airway tone and is secreted from tracheal and bronchial epithelial cells (Black et al, 1989;Mattoli et al, 1990), endothelins may play an active role in diseases such as asthma, bronchitis and adult respiratory distress syndrome. These airway diseases are associated with vascular remodelling, reduction of airway calibre, increased microvascular permeability, ciliary function, ion transport and mucin release which are all affected by the endothelins (Wu et al, 1990;Tamaoki et al, 1991;Plews et al, 1991;Peacock et al, 1992;Helset et al, 1993). The ability of PD 145065 to antagonize ET-1 in airway tissues therefore suggests it may be beneficial in disease states.…”

Section: Discussionmentioning

confidence: 99%

Characterization of ET_B receptors mediating contractions induced by endothelin‐1 or IRL 1620 in guinea‐pig isolated airways: effects of BQ‐123, FR139317 or PD 145065

Battistini

Warner

Fournier

et al. 1994

British J Pharmacology

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We have characterized the receptors mediating contractions to endothelin‐1 (ET‐1) or IRL 1620, an ETB receptor selective agonist, in isolated strips of tissue prepared from different parts of the guinea‐pig airways. We used as antagonists BQ‐123 and FR139317 (ETA receptor‐selective) and PD 145065 (ETA/ETB receptor non‐selective). ET‐1 and IRL 1620 (10−10 m to 10−6 m) caused similar concentration‐dependent contractions of strips of guinea‐pig trachea and upper bronchus. In the guinea‐pig trachea without epithelium or lung parenchyma, IRL 1620 was less potent than ET‐1. In the trachea, contraction to ET‐1 (< 10−8 m) was preceded by a transient relaxation which was inhibited by BQ‐123 (10−5 m) or FR 139317 (10−5 m) or by the removal of the epithelium. The concentration‐response curve to ET‐1 in the trachea was shifted to the right by PD 145065 (10−5 m to 10−4 m). PD 145065 (10−4 m) also inhibited the response to ET‐1 (3 × 10−7 m) by 55%. Contractions induced by IRL 1620 were not affected by BQ‐123 (10−6 m) or FR139317 (10−6 m) but were significantly attenuated by 10−5 m of either antagonist. PD 145065 at 10−6 m strongly attenuated and at 10−5 m abolished contractions induced by IRL 1620. In the trachea, removal of the epithelium potentiated the effects of both agonists. BQ‐123 (10−5 m) had no effect on contractions of the trachea without epithelium induced by ET‐1, but FR139317 (10−5 m) caused a significant inhibition. PD 145065 (10−5 m to 10−4 m) caused a shift to the right of the ET‐1 concentration‐response curve without affecting the contractile effect at 3 × 10−7 m. All three antagonists inhibited contractions induced by IRL 1620. In the upper bronchus, BQ‐123 (10−5 m) did not affect contractions induced by ET‐1, while FR139317 (10−5 m) attenuated (20–26%) only contractions induced by 1–3 × 10−7 m ET‐1. PD 145065 (10−5 m to 10−4 m) caused a shift to the right of the ET‐1 concentration‐response curve. The contractions induced by IRL 1620 were inhibited by BQ‐123 or FR139317 (10−5 m to 10−4 m). PD 145065 (10−6 m) strongly inhibited contractions induced by IRL 1620 and PD 145065 (10−5 m) totally abolished them. The contractile action of ET‐1 in the lung parenchyma was significantly and similarly attenuated by BQ‐123 (10−5 m) or indomethacin (10−5 m), while FR139317 (10−5 m) was less effective. PD 145065 (10−6 to 10−5 m) inhibited contractions to ET‐1. IRL 1620, which is less potent than ET‐1 in this preparation, was antagonized by PD 145065 (10−5 to 10−6 m) but unaffected by BQ‐123 (10−6 m to 10−5 m) or FR139317 (10−6 m). Thus, ETB receptors mediate contractions to ET‐1 in all four guinea‐pig airway preparations. In addition, contractions to ET‐1 in the trachea and lung parenchyma are mediated in part by ETA receptors. In the latter tissue, these ETA receptors mediate contraction through the release of cyclo‐oxygenase metabolites. Similarly, ETA receptors located on the epithelial cells also mediate the release of prostanoids in the trachea with epithelium but they are responsible for transient relaxations. Intere...

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Endothelin-1 Stimulates Eicosanoid Production in Cultured Human Nasal Mucosa

Cited by 40 publications

References 41 publications

Relative contributions of direct and indirect mechanisms mediating endothelin‐induced contraction of guinea‐pig trachea

Relative contributions of direct and indirect mechanisms mediating endothelin‐induced contraction of guinea‐pig trachea

Erythromycin and clarithromycin attenuate cytokine-induced endothelin-1 expression in human bronchial epithelial cells

Characterization of ET_B receptors mediating contractions induced by endothelin‐1 or IRL 1620 in guinea‐pig isolated airways: effects of BQ‐123, FR139317 or PD 145065

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Endothelin-1 Stimulates Eicosanoid Production in Cultured Human Nasal Mucosa

Cited by 40 publications

References 41 publications

Relative contributions of direct and indirect mechanisms mediating endothelin‐induced contraction of guinea‐pig trachea

Relative contributions of direct and indirect mechanisms mediating endothelin‐induced contraction of guinea‐pig trachea

Erythromycin and clarithromycin attenuate cytokine-induced endothelin-1 expression in human bronchial epithelial cells

Characterization of ETB receptors mediating contractions induced by endothelin‐1 or IRL 1620 in guinea‐pig isolated airways: effects of BQ‐123, FR139317 or PD 145065

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Characterization of ET_B receptors mediating contractions induced by endothelin‐1 or IRL 1620 in guinea‐pig isolated airways: effects of BQ‐123, FR139317 or PD 145065