Document Detail


Conversion of big ET-1 in the rat lung: role of phosphoramidon-sensitive endothelin-1-converting enzyme.
MedLine Citation:
PMID:  8141343     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
We examined conversion of Big endothelin-1 (ET-1) to mature ET-1 and pressor action during perfusion of the isolated perfused rat lung with Big ET-1. Big ET-1 caused a concentration-related increase in perfusion pressure and the pressor molar potency of the peptide was fivefold less than that of ET-1. Pressor responses to Big ET-1 were accompanied by an increase in immunoreactive-ET (IR-ET) levels in the perfusate and in the lung tissues. Pretreatment with phosphoramidon (10(-4) M), a metalloproteinase inhibitor, markedly suppressed the pressor action and increment in IR-ET in the tissues. Unexpectedly, the amount of IR-ET in the perfusate during perfusion of Big ET-1 was not influenced by phosphoramidon treatment. On the other hand, chymostatin, an inhibitor of chymotrypsin-like enzymes, effectively suppressed IR-ET levels in the perfusate; however, this enzyme inhibitor was without effect on the pressor action of Big ET-1 or on the increase in IR-ET levels in lung tissues. We tentatively conclude that the phosphoramidon-sensitive conversion of Big ET-T to ET-1 is linked to the pressor action of Big ET-1 in the isolated perfused rat lung. In addition, it seems likely that chymostatin-sensitive conversion of Big ET-1 to ET-1 does not play a major role in the conversion of the precursor to the mature form. We propose that IR-ET present in the tissues rather than that in the perfusate is a better indicator of the functional conversion of Big ET-1 in the rat lung.
Authors:
K Hisaki; Y Matsumura; H Maekawa; K Fujita; M Takaoka; S Morimoto
Related Documents :
1810373 - Euro-collins solution versus uw-solution for long-term liver preservation in the isolat...
20732133 - Influence of oxygen supply on liver condition and elimination of dimethylacetamide in t...
9290463 - Plasma endothelin-1 and tumor necrosis factor-alpha concentrations in pregnant and cycl...
Publication Detail:
Type:  In Vitro; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The American journal of physiology     Volume:  266     ISSN:  0002-9513     ISO Abbreviation:  Am. J. Physiol.     Publication Date:  1994 Feb 
Date Detail:
Created Date:  1994-04-26     Completed Date:  1994-04-26     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  0370511     Medline TA:  Am J Physiol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  H422-8     Citation Subset:  IM    
Affiliation:
Department of Pharmacology, Osaka University of Pharmaceutical Sciences, Japan.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Animals
Aspartic Acid Endopeptidases / metabolism*
Chymotrypsin / antagonists & inhibitors
Dose-Response Relationship, Drug
Endothelin-1
Endothelins / metabolism*,  pharmacology*
Glycopeptides / pharmacology*
Kinetics
Lung / drug effects,  enzymology,  physiology*
Male
Metalloendopeptidases / antagonists & inhibitors*
Oligopeptides / pharmacology
Perfusion
Protein Precursors / metabolism
Pulmonary Circulation / drug effects,  physiology*
Rats
Rats, Sprague-Dawley
Chemical
Reg. No./Substance:
0/Endothelin-1; 0/Endothelins; 0/Glycopeptides; 0/Oligopeptides; 0/Protein Precursors; 36357-77-4/phosphoramidon; 9076-44-2/chymostatin; EC 3.4.21.1/Chymotrypsin; EC 3.4.23.-/Aspartic Acid Endopeptidases; EC 3.4.24.-/Metalloendopeptidases; EC 3.4.24.71/endothelin-converting enzyme

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Circulating neutrophil kinetics during tolerance in hemorrhagic shock using bacterial lipopolysaccha...
Next Document:  Plasma norepinephrine variations correlate with peripheral vascular resistance in resting humans.