Switch to
Predicate | Object |
---|---|
rdf:type | |
lifeskim:mentions | |
pubmed:dateCreated |
1996-3-28
|
pubmed:abstractText |
We developed a procedure for individual measurement of big endothelin-1 (big ET-1) and the two products of big ET-1 conversion (ET-1 and C-terminal fragment (CTF) of big ET-1 (big ET-1(22-38)), using selective solid-phase extraction and specific radioimmunoassays. These techniques were used to measure the levels of these peptides in extracts of human plasma after brachial artery infusions of big ET-1. Infusion of big ET-1 (50 pmol/min, n = 6) caused a decrease in forearm blood flow from 3.03 to 1.55 ml/dl/min after 60 min (p < 0.05). In agreement, the levels of plasma immunoreactive (IR) big ET-1, ET, and CTF were significantly increased from basal levels in the infused arm (from undetectable to 386 pM, 2.2-7.5 pM, and 0.17-37 pM, respectively; p < 0.05). In the presence of the metalloprotease inhibitor phosphoramidon (30 nmol/min), the increase in IR-ET and the associated vasoconstriction were abolished. However, IR-CTF was still detected, suggesting that either some conversion by phosphoramidon-insensitive endothelin-converting enzyme (ECE) was occurring and/or that CTF was being preserved from further proteolysis by phosphoramidon. These data confirm that exogenous big ET-1 is locally converted to ET-1 and CTF in the human forearm, at least in part by a phosphoramidon-sensitive ECE. Furthermore, because measurable levels of newly synthesized ET-1 are probably rapidly reduced as a result of receptor binding, the assay of IR-CTF may be a more sensitive measure of the overexpression of ET-1 in disease.
|
pubmed:language |
eng
|
pubmed:journal | |
pubmed:citationSubset |
IM
|
pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Aspartic Acid Endopeptidases,
http://linkedlifedata.com/resource/pubmed/chemical/Endothelin-1,
http://linkedlifedata.com/resource/pubmed/chemical/Endothelins,
http://linkedlifedata.com/resource/pubmed/chemical/Glycopeptides,
http://linkedlifedata.com/resource/pubmed/chemical/Metalloendopeptidases,
http://linkedlifedata.com/resource/pubmed/chemical/Peptide Fragments,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Precursors,
http://linkedlifedata.com/resource/pubmed/chemical/endothelin-converting enzyme,
http://linkedlifedata.com/resource/pubmed/chemical/phosphoramidon
|
pubmed:status |
MEDLINE
|
pubmed:issn |
0160-2446
|
pubmed:author | |
pubmed:issnType |
Print
|
pubmed:volume |
26 Suppl 3
|
pubmed:owner |
NLM
|
pubmed:authorsComplete |
Y
|
pubmed:pagination |
S34-6
|
pubmed:dateRevised |
2009-11-19
|
pubmed:meshHeading |
pubmed-meshheading:8587408-Adult,
pubmed-meshheading:8587408-Aspartic Acid Endopeptidases,
pubmed-meshheading:8587408-Endothelin-1,
pubmed-meshheading:8587408-Endothelins,
pubmed-meshheading:8587408-Glycopeptides,
pubmed-meshheading:8587408-Humans,
pubmed-meshheading:8587408-Male,
pubmed-meshheading:8587408-Metalloendopeptidases,
pubmed-meshheading:8587408-Peptide Fragments,
pubmed-meshheading:8587408-Protein Precursors,
pubmed-meshheading:8587408-Vasoconstriction
|
pubmed:year |
1995
|
pubmed:articleTitle |
Measurement of C-terminal fragment of big endothelin-1: a novel method for assessing the generation of endothelin-1 in humans.
|
pubmed:affiliation |
Clinical Pharmacology Unit, University of Cambridge, Addenbrooke's Hospital, England.
|
pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
|