Mechanical and biochemical responses to endothelin-1 and endothelin-3 in human bronchi

Nally, Jane E.; McCall, Raymond; Young, Louise; Wakelam, Michael J.O.; Thomson, Neil C.; McGrath, J.C.

doi:10.1016/0922-4106(94)90009-4

Cited by 18 publications

(13 citation statements)

References 34 publications

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“…Nally and co-workers (1994) reported that in bronchial tissue (third to sixth order) from patients undergoing surgery, ET-1-induced contractions were not inhibited by nifedipine (10 µM). Furthermore, a single concentration of ET-1 (0.3 µM) produced a rapid, marked increase (about 250%) in IP 3 levels, and it was concluded that ET-1 induces contraction via mobilization of Ca 2+ from intracellular sources, with no influence of influx through voltage-dependent, dihydropyri-dine-sensitive membrane channels (Nally et al 1994). In human cultured bronchial smooth muscle cells ET-1 increased cytoplasmic Ca 2+ biphasically, reflecting mobilization of Ca 2+ from extracellular and intracellular pools, and stimulated inositol phosphates and diacylglycerol (Mattoli et al 1991).…”

Section: Discussionmentioning

confidence: 99%

“…In contrast, ET A receptor-induced contraction in rat tracheal smooth muscle was dependent upon the release of intracellular Ca 2+ , whereas that elicited by ET B receptor activation was abolished upon removal of extracellular Ca 2+ (Henry 1993). McKay et al (1991) and Nally et al (1994) reported that ET-1-induced human bronchial smooth muscle contraction was independent of the influx of extracellular Ca 2+ via dihydopyridine-sensitive calcium channels. The aim of the present study was to explore further, using functional and biochemical techniques, selective ET ligands and inhibitors of calcium translocation pathways, the role of Ca 2+ in ETinduced contraction in human bronchus.…”

Section: Introductionmentioning

confidence: 99%

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Endothelin receptors and calcium translocation pathways in human airways

Hay¹,

Luttmann²,

Muccitelli³

et al. 1999

Naunyn-Schmiedeberg's Arch Pharmacol

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Tension and phosphatidyl inositol (PI) turnover experiments were conducted to investigate the receptors and signal transduction pathways responsible for contractions elicited by endothelin (ET) ligands in human bronchus. Nicardipine (1 microM), the L-type calcium channel inhibitor, or incubation in Ca2+-free medium, produced marked inhibition of contractions to the ET(B) receptor-selective agonist, sarafotoxin S6c, and especially those induced by KCl. In contrast, Ca2+-free medium was without appreciable effect against contraction produced by endothelin-1 (ET-1), the non-selective ET(A) and ET(B) receptor agonist. In Ca2+-free medium, ryanodine (10 microM), which inhibits intracellular calcium mobilization, reduced sarafotoxin S6c- and ET-1-induced responses, but was without effect on responses to KCl. Similarly, nickel chloride (Ni2+; 1 mM) caused marked inhibition of contractions induced by sarafotoxin S6c or ET-1, but had no significant effect on KCI concentration-response curves. The mixed ET(A)/ET(B) receptor antagonist SB 209670 (3 microM) inhibited responses to sarafotoxin S6c and ET-1 such that concentration-response curves were shifted rightward, at the 30% maximum response level, by 10.0- and 3.8-fold, respectively, whereas BQ-123 (3 microM), the ET(A) receptor antagonist, was without effect on responses induced by either agonist. ET-1 (1 nM-0.3 microM) caused a concentration-dependent stimulation of PI turnover, whereas sarafotoxin S6c (0.3 nM-0.1 microM) induced only small and variable increases, except at the highest concentration. The increase in PI turnover evoked by ET-1 was inhibited by SB 209670 (3 microM), and also by BQ-123 (3 microM). This is consistent with linkage of ET(A) receptors to activation of inositol phosphate generation in human bronchial smooth muscle cells. Collectively, the data suggest that differences exist in the relative contributions of intracellular and extracellular Ca2+ mobilization mechanisms elicited by ET(A) and ET(B) receptor activation. Thus, sarafotoxin S6c-induced, ET(B) receptor-mediated contraction in human bronchial smooth muscle appears to be dependent, in part, upon extracellular Ca2+, although a significant component of the response was also mediated by intracellular Ca2+ release, including from ryanodine-sensitive stores. ET(A) receptor-mediated contraction of human airway smooth muscle was activated largely via the release of intracellular Ca2+.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Endothelin receptors and calcium translocation pathways in human airways

Hay¹,

Luttmann²,

Muccitelli³

et al. 1999

Naunyn-Schmiedeberg's Arch Pharmacol

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“…Specific radioimmunoassay has demonstrated raised venous plasma levels of ET-1 in IPAH, associated causes and secondary causes when compared to healthy volunteers [39]. ET-1 can also cause bronchoconstriction both in vitro [40], and in vivo when inhaled by asthmatics [41]. ET-1 has also been found in bronchoalveolar lavage samples of COPD patients [42], and in greater concentration in patients with cystic fibrosis in induced sputum samples [43].…”

Section: Spirometry and Expiratory Flowmentioning

confidence: 95%

Lung function in pulmonary hypertension

Low

Medford

Millar

et al. 2015

Respiratory Medicine

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Breathlessness is a common symptom in pulmonary hypertension (PH) and an important cause of morbidity. Though this has been attributed to the well described pulmonary vascular abnormalities and subsequent cardiac remodelling, changes in the airways of these patients have also been reported and may contribute to symptoms. Our understanding of these airway abnormalities is poor with conflicting findings in many studies. The present review evaluates these studies for the major PH groups. In addition we describe the role of cardiopulmonary exercise testing in the assessment of pulmonary arterial hypertension (PAH) by evaluating cardiopulmonary interaction during exercise. As yet, the reasons for the abnormalities in lung function are unclear, but potential causes and the possible role of inflammation are discussed. Future research is required to provide a better understanding of this to help improve the management of these patients.

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“…Endothelin-1 has also been observed to contribute to mucus hypersecretion promoting airway microvascular leakage and edema (Goldie and Fernandes 2000). Moreover, endothelin-1 has been shown to be highly potent bronchoconstrictor acting on airway smooth muscle in human bronchi as well as in patients with asthma (Chalmers et al 1997;Nally et al 1994;Springall et al 1991;Trakada et al 2001). Although circulating blood concentrations are poor indicators of specific tissue concentrations, it is unlikely that the present changes in endothelin-1 levels had a significant impact on airway function.…”

Section: Discussionmentioning

confidence: 97%

“…Endothelin-1, a potent pulmonary vasoconstrictor peptide that also augments microvascular permeability (Chalmers et al 1997;Goldie and Fernandes 2000;Nally et al 1994;Springall et al 1991;Trakada et al 2001), was measured by a quantitative two-site chemiluminescent immunoassay (R & D Systems, Minneapolis, MN). Plasma catecholamines, which induce bronchodilation and interstitial fluid clearance (Mazzeo et al 1994;Milic-Emili et al 2001;Sartori et al 2002), were measured by reversed phase HPLC with electrochemical detection after extraction with activated alumina.…”

Section: Study Design and Measurementsmentioning

confidence: 99%

Variability in pulmonary function following rapid altitude ascent to the Amundsen–Scott South Pole station

et al. 2011

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The impact of acute altitude exposure on pulmonary function is variable. A large inter-individual variability in the changes in forced expiratory flows (FEFs) is reported with acute exposure to altitude, which is suggested to represent an interaction between several factors influencing bronchial tone such as changes in gas density, catecholamine stimulation, and mild interstitial edema. This study examined the association between FEF variability, acute mountain sickness (AMS) and various blood markers affecting bronchial tone (endothelin-1, vascular endothelial growth factor (VEGF), catecholamines, angiotensin II) in 102 individuals rapidly transported to the South Pole (2835 m). The mean FEF between 25 and 75% (FEF(25-75)) and blood markers were recorded at sea level and after the second night at altitude. AMS was assessed using Lake Louise questionnaires. FEF(25-75) increased by an average of 12% with changes ranging from -26 to +59% from sea level to altitude. On the second day, AMS incidence was 36% and was higher in individuals with increases in FEF(25-75) (41 vs. 22%, P = 0.05). Ascent to altitude induced an increase in endothelin-1 levels, with greater levels observed in individuals with decreased FEF(25-75). Epinephrine levels increased with ascent to altitude and the response was six times larger in individuals with decreased FEF(25-75). Greater levels of endothelin-1 in individuals with decreased FEF(25-75) suggest a response consistent with pulmonary hypertension and/or mild interstitial edema, while epinephrine may be upregulated in these individuals to clear lung fluid through stimulation of β(2)-adrenergic receptors.

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Mechanical and biochemical responses to endothelin-1 and endothelin-3 in human bronchi

Cited by 18 publications

References 34 publications

Endothelin receptors and calcium translocation pathways in human airways

Endothelin receptors and calcium translocation pathways in human airways

Lung function in pulmonary hypertension

Variability in pulmonary function following rapid altitude ascent to the Amundsen–Scott South Pole station

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