Document Detail


Amiloride analogs induce the phosphorylation of elongation factor-2 in vascular endothelial cells.
MedLine Citation:
PMID:  2359404     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
5-(N-Ethyl-N-isopropyl)amiloride (EIPA), a potent inhibitor of Na+/H+ antiport, reduced [35S]methionine incorporation in proteins and induced the phosphorylation of a Mr 95,000 protein in bovine aortic endothelial cells. This protein was previously shown to become phosphorylated in response to ATP, bradykinin, and A23187 (1) and was identified as elongation factor-2 (2). The action of EIPA was independent of changes in cytosolic pH, because it was neither mimicked by sodium acetate nor inhibited by ammonium chloride, and it was reproduced by 2',4'-dimethylbenzamil, an analog of amiloride that is inactive on the Na+/H+ antiport. Furthermore, EIPA enhanced the Ca2(+)-dependent phosphorylation of a similar Mr 95,000 protein in a cell-free system, rabbit reticulocyte lysate, where an inhibitory effect of amiloride on protein synthesis has already been described (3). Because phosphorylation decreases the activity of elongation factor-2, our observation might explain why amiloride analogs inhibit protein synthesis.
Authors:
D Demolle; M Lecomte; O Boutherin-Falson; E J Cragoe; A C Nairn; J M Boeynaems
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Molecular pharmacology     Volume:  37     ISSN:  0026-895X     ISO Abbreviation:  Mol. Pharmacol.     Publication Date:  1990 Jun 
Date Detail:
Created Date:  1990-08-01     Completed Date:  1990-08-01     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0035623     Medline TA:  Mol Pharmacol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  827-32     Citation Subset:  IM    
Affiliation:
Institute of Interdisciplinary Research, School of Medicine, Université Libre de Bruxelles, Belgium.
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MeSH Terms
Descriptor/Qualifier:
Amiloride / analogs & derivatives*,  pharmacology
Animals
Cattle
Cells, Cultured
Endothelium, Vascular / drug effects,  metabolism*
Hydrogen-Ion Concentration
Kinetics
Methionine / metabolism
Molecular Weight
Peptide Elongation Factor 2
Peptide Elongation Factors / metabolism*
Phosphorylation
Reticulocytes / drug effects,  metabolism*
Ribonucleoproteins / metabolism
Chemical
Reg. No./Substance:
0/Peptide Elongation Factor 2; 0/Peptide Elongation Factors; 0/Ribonucleoproteins; 1154-25-2/ethylisopropylamiloride; 2609-46-3/Amiloride; 63-68-3/Methionine

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