Tissue distribution and half-life of 125 I-endothelin in the rat: Importance of pulmonary clearance

Sirviö, Marja-Leena; Metsärinne, Kaj; Saijonmaa, Outi; Fyhrquist, Frej

doi:10.1016/0006-291x(90)90649-8

Cited by 109 publications

(50 citation statements)

References 9 publications

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“…Incubation of unlabelled ET-1 with purified cathepsin G allowed to identify a major cleavage site corresponding to the Hisl6-Leu x7 bond, leading to the formation of inactive [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16] fragments and the C-terminal pentapeptide.…”

Section: Discussionmentioning

confidence: 99%

“…This specificity is observed in the hydrolysis of the His-Leu bond of ET-1. The cleavage of this bond, generating [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16] fragments and the C-terminal pentapeptide (Table I) is sufficient to induce a biological activity loss of ET-1. Indeed, we have previously shown that [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16] peptides, resulting from the hydrolysis of ET-1 by endopeptidase 24.11, were devoid of vasoconstrictor effect on isolated rat aortic rings [9].…”

Section: Discussionmentioning

confidence: 99%

“…5). They were collected and submitted to amino acid analysis, Peaks 1, 2, 3 had amino acid compositions compatible with the sequence ET-1 [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16] and probably differed from each other by additional cleavages in the disulfidelinked loops (Table I) had a composition identical to that of ET-1 and might differ from the intact substrate by one or more cleavages inside the disulfide-linked loops. Peak 6 was present as a double peak due to the appearance of a metabolite not resolved from ET-1.…”

Section: Hydrolysis Of Unlabelled Et-1 By Cathepsin Gmentioning

confidence: 99%

“…Injected in rat circulation, ET peptides disappear with a very short half-life [6,7]. In man, the disappearance curve of perfused endothelin-1 exhibit two half-lives of 1.4 and 35 min, respectively [8].…”

Section: Introductionmentioning

confidence: 99%

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Enzymatic degradation of endothelin-1 by activated human polymorphonuclear neutrophils

Fagny¹,

Michel²,

Nortier³

et al. 1992

Regulatory Peptides

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SummaryEndothelin-1 (ET-1) is a potent vasoconstrictor peptide secreted by endothelial cells. We investigated whether polymorphonuclear neutrophils (PMN) were able to destroy this peptide by enzymatic hydrolysis produced either by the membrane-bound endopeptidase 24.11 or by lysosomal proteinases released in the medium by activated cells. Resting and activated PMN were incubated with 125I-labelled ET-1 and the degradation fragments were analyzed by HPLC. A marked degradation of ET-1 was observed only in the presence of the stimulated cells, leading to the generation of seven radiolabelled peaks. Addition of phosphoramidon had no effect on the appearance of these metabolites, while soybean trypsin inhibitor abolished almost completely the degradation of the peptide, suggesting a role of cathepsin G in ET-1 hydrolysis.Among the purified leukocyte enzymes tested, cathepsin G hydrolyzed 125I-labelled ET-1 at the higher rate and gave rise to two radiolabelled peaks already observed in the presence of activated PMN. Incubation of unlabelled ET-1 with purified cathepsin G allowed to identify a major cleavage site corresponding to the Hisl6-Leu x7 bond, leading to the formation of inactive [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16] fragments and the C-terminal pentapeptide.This mechanism of ET-1 inactivation could play a role in acute inflammatory reaction where PMN adhere to the vascular endothelial cells.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Hydrolysis Of Unlabelled Et-1 By Cathepsin Gmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Enzymatic degradation of endothelin-1 by activated human polymorphonuclear neutrophils

Fagny¹,

Michel²,

Nortier³

et al. 1992

Regulatory Peptides

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“…However, ET-1 release is difficult to measure due its short half-life [20], receptor binding during pulmonary passage [21], and cleavage by neutral endopeptidases [22]. Recently, a novel assay for measurement of the more stable C-terminal ET-1 precursor fragment [C-terminal-pro-endothelin-1 (CT-proET-1)] has become available [20].…”

Section: Introductionmentioning

confidence: 99%

B‐type natriuretic peptide and C‐terminal‐pro‐endothelin‐1 for the prediction of severely impaired peak oxygen consumption

Maeder

Brutsche

Staub

et al. 2009

Journal of Internal Medicine

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Objective. To assess the utility of B-type natriuretic peptide (BNP) and C-terminal-pro-endothelin-1 (CTproET-1) to predict a severely impaired peak oxygen consumption (peak VO 2 , < 14 mL kg )1 min )1 ) in patients referred for cardiopulmonary exercise testing.Design. Cross-sectional study.Setting. Tertiary care center.Methods. Peak VO 2 , BNP and CT-proET-1 were assessed in 141 consecutive patients referred for cardiopulmonary exercise testing.Results. B-type natriuretic peptide [median (interquartile range) 48 (38-319) vs. 33 (15-86) pg mL )1 ; P = 0.002] and vs. 60 (52-74) pmol L )1 ; P < 0.001] were higher in patients with a peak VO 2 < 14 mL kg )1 min )1 (n = 30) than in those with a peak VO 2 ‡ 14 mL kg )1 min )1 (n = 111). CT-pro-ET-1 had a higher area under the receiver-operator-characteristics curve (AUC) to predict a peak VO 2 < 14 mL kg )1 min )1 than BNP (0.79 vs. 0.68; P = 0.04). The optimal BNP cut-off of 37.2 pg mL )1 had a sensitivity of 80% and a specificity of 56%. The optimal CT-proET-1 cut-off of 74.4 pmol L )1 had a sensitivity of 80% and specificity of 76%. A five-item score composed of body mass index, diabetes, forced expiratory volume within the first second, alveolo-arterial oxygen pressure difference, and BNP had an AUC of 0.88 to predict a peak VO 2 < 14 mL kg )1 min )1 . Adding CT-proET-1 to the score resulted in an AUC of 0.92.Conclusions. C-terminal-pro-endothelin-1 is superior to BNP for the prediction of a peak VO 2 < 14 mL kg )1 min )1 in patients referred for CPET. A score incorporating body mass index, diabetes status, spirometry, blood gases, BNP and CT-proET-1 improves the prediction of a peak VO 2 < 14 mL kg )1 min )1 based on single biomarkers.

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The role of endothelins and their receptors in heart failure

Giannessi

Vitale

2001

Pharmacological Research

100

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Tissue distribution and half-life of 125 I-endothelin in the rat: Importance of pulmonary clearance

Cited by 109 publications

References 9 publications

Enzymatic degradation of endothelin-1 by activated human polymorphonuclear neutrophils

Enzymatic degradation of endothelin-1 by activated human polymorphonuclear neutrophils

B‐type natriuretic peptide and C‐terminal‐pro‐endothelin‐1 for the prediction of severely impaired peak oxygen consumption

The role of endothelins and their receptors in heart failure

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