PT  - JOURNAL ARTICLE
AU  - D Demolle
AU  - M Lecomte
AU  - O Boutherin-Falson
AU  - E J Cragoe, Jr
AU  - A C Nairn
AU  - J M Boeynaems
TI  - Amiloride analogs induce the phosphorylation of elongation factor-2 in vascular endothelial cells.
DP  - 1990 Jun 01
TA  - Molecular Pharmacology
PG  - 827--832
VI  - 37
IP  - 6
4099  - http://molpharm.aspetjournals.org/content/37/6/827.short
4100  - http://molpharm.aspetjournals.org/content/37/6/827.full
SO  - Mol Pharmacol1990 Jun 01; 37
AB  - 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.