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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
4
|
| pubmed:dateCreated |
1995-7-11
|
| pubmed:abstractText |
1. In vivo the effects of endothelin-1 (ET-1) are limited by its rapid removal from the circulation and possibly by its metabolism by enzymes such as neutral endopeptidase 24.11, deamidase or carboxypeptidase A. Here, using as a model the isolated perfused mesenteric arterial bed of the rat, we have examined the involvements of these enzymatic activities in the vascular responses to ET-1. 2. Samples of Krebs buffer which had been recirculated through the mesenteric arterial bed for 30 min rapidly destroyed the activity of ET-1 as assessed either by bioassay on rings of rat thoracic aorta or by high performance liquid chromatography (h.p.l.c.). For instance, after 15 min incubation with the recirculated-Krebs solution (recirc-K) the contraction induced by 3 x 10(-9) M ET-1 was reduced by more than 90%. Contractions induced by sarafotoxin 6b (3 x 10(-9) M) were similarly suppressed by preincubation with recirc-K whereas those to Arg-vasopressin (3 x 10(-9) M) were unaffected. 3. The degradation of ET-1 by recirc-K was prevented by 1,10-phenanthroline (10(-3) M), abolished by heating the recirc-K solution to 90 degrees C for 15 min, and reduced by EGTA (5 x 10(-3) M) or ET-1(16-21) (10(-5) M). For instance, in the presence of ET-1(16-21) (n = 6) the contraction induced by ET-1 was reduced by only 40% after 15 min incubation with recirc-K buffer. Leupeptin (3 x 10-4 M), dichloroisocoumarin(5 x 10-5 M), phenylmethyl-sulphonyl fluoride (10-3 M), a combination of bacitracin (300 mg ml-1),bestatin (10-5 M), captopril (10-5 M), phosphoramidon (10-4 M) and thiorphan (10-4 M) or Polypep (aproprietary protein digest) did not inhibit the degradation of ET-1 by recirc-K.4. In experiments examining directly the vascular responses of the isolated perfused mesentery of the rat, the addition of cumulative concentrations of ET-1 to the recirculating Krebs solution caused small concentration-dependent increases in perfusion pressure. The inclusion of ET-1(16-2l), ET-1(17-21), or ET-1(18-21) (10-5M) greatly potentiated these responses, but not those to Arg-vasopressin or methoxamine.The effects of 1,10-phenanthroline or EGTA could not be examined in this system because these agents both depressed non-specifically the vasoconstrictor responses of the mesenteric vascular bed.5. Thus, the rat mesentery releases an enzyme that very rapidly destroys ET-1 or the very closely related peptide, sarafotoxin 6b but not Arg-vasopressin. This enzyme is most probably a metallopeptidase because of its sensitivity to inhibition by 1,10-phenanthroline or EGTA. It is particularly interesting that a simple vascular bed such as the mesentery produces such a powerful endothelin metabolising enzyme. It is tempting, therefore, to speculate that the endothelin degrading enzyme active at neutral pH that- we have found is important in the metabolism of ET-1 throughout the vasculature.
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| pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/7773548-1371751,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7773548-1429507,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7773548-14296957,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7773548-1447951,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7773548-1737744,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7773548-2191299,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7773548-2201681,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7773548-2328405,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7773548-2451132,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7773548-2473326,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7773548-2693125,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7773548-3056409,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7773548-3059352,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7773548-7510002,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7773548-7519527,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7773548-8019501,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7773548-8032643,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7773548-8064161,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7773548-8096364,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7773548-8188617,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7773548-8505102
|
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/1,10-phenanthroline,
http://linkedlifedata.com/resource/pubmed/chemical/Arginine Vasopressin,
http://linkedlifedata.com/resource/pubmed/chemical/Carboxypeptidases,
http://linkedlifedata.com/resource/pubmed/chemical/Carboxypeptidases A,
http://linkedlifedata.com/resource/pubmed/chemical/Endothelins,
http://linkedlifedata.com/resource/pubmed/chemical/Metalloendopeptidases,
http://linkedlifedata.com/resource/pubmed/chemical/Neprilysin,
http://linkedlifedata.com/resource/pubmed/chemical/Nicotinamidase,
http://linkedlifedata.com/resource/pubmed/chemical/Phenanthrolines
|
| pubmed:status |
MEDLINE
|
| pubmed:month |
Feb
|
| pubmed:issn |
0007-1188
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| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:volume |
114
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
867-71
|
| pubmed:dateRevised |
2009-11-18
|
| pubmed:meshHeading |
pubmed-meshheading:7773548-Animals,
pubmed-meshheading:7773548-Aorta, Thoracic,
pubmed-meshheading:7773548-Arginine Vasopressin,
pubmed-meshheading:7773548-Carboxypeptidases,
pubmed-meshheading:7773548-Carboxypeptidases A,
pubmed-meshheading:7773548-Chromatography, High Pressure Liquid,
pubmed-meshheading:7773548-Endothelins,
pubmed-meshheading:7773548-Male,
pubmed-meshheading:7773548-Mesenteric Arteries,
pubmed-meshheading:7773548-Metalloendopeptidases,
pubmed-meshheading:7773548-Muscle, Smooth, Vascular,
pubmed-meshheading:7773548-Muscle Contraction,
pubmed-meshheading:7773548-Neprilysin,
pubmed-meshheading:7773548-Nicotinamidase,
pubmed-meshheading:7773548-Perfusion,
pubmed-meshheading:7773548-Phenanthrolines,
pubmed-meshheading:7773548-Rats,
pubmed-meshheading:7773548-Rats, Wistar,
pubmed-meshheading:7773548-Vasoconstriction
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| pubmed:year |
1995
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| pubmed:articleTitle |
Rapid degradation of endothelin-1 by an enzyme released by the rat isolated perfused mesentery.
|
| pubmed:affiliation |
William Harvey Research Institute, Medical College of Saint Bartholomews' Hospital, London.
|
| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
|