Disease relevance of Ethylisopropylamiloride

• These findings are consistent with short-term exposure to EIPA accelerating ATP depletion during ischemia, as well as limiting proton efflux during reperfusion [1].
• 6. In CO2-HCO3(-)-buffered Tyrode solution, pHi recovery from an intracellular acidosis (NH4+ pre-pulse) was only partially inhibited by EIPA or amiloride whereas Nao+ removal completely inhibited the recovery [2].
• OBJECTIVE: The aim was to investigate the effect of ethylisopropylamiloride (EIPA), an inhibitor of Na+/H+ exchange, and of extracellular pH on the proliferation of immortalised lymphoblasts derived from patients with essential hypertension and normotensive controls [3].
• Addition of 1 x 10(-5) mol/l amiloride or 3 x 10(-7) mol/l 5-(N-ethyl-N-isopropyl)amiloride (EIPA) markedly decreased the incidence and duration of ventricular fibrillation or even suppressed fibrillation completely as in the case of 1 x 10(-6) mol/l EIPA [4].
• 3. Release is also enhanced by lignocaine but inhibited by amiloride and ethylisopropylamiloride, suggesting that sodium entry into adrenergic nerve terminals during anoxia occurs by Na+/H+ (and possibly Na+/Ca2+) exchange [5].

High impact information on Ethylisopropylamiloride

• The ethylisopropylamiloride sensitivity of the Na/H antiporters were different in these two cell lines (MCT IC50 = 65 nM; OKP IC50 = 4.5 microM) [6].
• The stimulatory effect of the calmodulin antagonist calmidazolium (10 microM) on renin secretion was not altered by endothelial cells, whereas the stimulatory effect of ethylisopropylamiloride (50 microM) an inhibitor of sodium-proton exchange was enhanced in the presence of endothelial cells [7].
• Here, stress fiber formation induced by p160ROCK was inhibited by the addition of a specific NHE1 inhibitor, ethylisopropylamiloride, in CCL39 fibroblasts, and was absent in PS120 mutant fibroblasts lacking NHE1 [8].
• Ethylisopropylamiloride, a specific inhibitor of the plasma membrane Na+/H+ antiporter, completely suppressed the effects of FN on both pHi and DNA synthesis [9].
• Both 1 microM amiloride and 0.1 microM benzamil inhibited 22Na uptake in mRNA-injected oocytes by greater than 95%, whereas less than 50% inhibition occurred with 1 microM 5-(N-ethyl-N-isopropyl)amiloride [10].

Chemical compound and disease context of Ethylisopropylamiloride

• 8. This was probably due to intracellular acidification, since acid-evoked secretion was enhanced by the Na+-H+ exchange blocker ethylisopropylamiloride (30 microM), and was mimicked by sodium propionate (10 mM), which causes selective intracellular acidosis [11].
• Following the acidosis pHi recovered in acini bathed in either control medium or Na(+)-free (Li+) medium, but not in acini bathed in Na(+)-free (NMDG) medium or in control medium containing EIPA [12].
• 5-(N-ethyl-N-isopropyl)amiloride and mild acidosis protect cultured cerebellar granule cells against glutamate-induced delayed neuronal death [13].
• In contrast, neomycin, U 73122, 5-(N-ethyl-N-isopropyl)amiloride or pertussis toxin were ineffective in blocking the potentiating effect of PAF [14].
• Inhibition of passive sodium ion transporters reduced cellular swelling during ischemia: pretreatment (10 min) with 100 microM furosemide (Na-K-2Cl cotransport), 1.5 microM ethylisopropylamiloride (Na/H antiport), and 50 microM lidocaine (sodium channels) led to swelling of 0.27, 0.21, and 0.13 ml/g dry wt, respectively [15].

Biological context of Ethylisopropylamiloride

• Recovery was inhibited by the Na+/H+ antiport inhibitor 5-(N-ethyl-N-isopropyl)amiloride (EIPA) [16].
• Videomicroscopy of MSV-MDCK-INV cells revealed that within 20 minutes of addition, ethylisopropylamiloride induced pseudopodial retraction and inhibited cell motility [17].
• 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 [18].
• In the normoxic heart EIPA produced a decrease in heart rate without producing any change either in myocardial energy metabolism or in pHi [19].
• A6 cells were found to express Na+/H(+)-exchange activity only on the basolateral membrane: Na+/H(+)-exchange activity follows simple saturation kinetics with an apparent Km for Na+ of approximately 11 mM; it is inhibited in a competitive manner by ethylisopropylamiloride (EIPA) [20].

Anatomical context of Ethylisopropylamiloride

• Intracellular pH in human arterial smooth muscle. Regulation by Na+/H+ exchange and a novel 5-(N-ethyl-N-isopropyl)amiloride-sensitive Na(+)- and HCO3(-)-dependent mechanism [21].
• After expression in exchanger-deficient fibroblasts (PS120), early response (< 80 s) to external stimuli was assessed as 5-(N-ethyl-N-isopropyl)amiloride-sensitive 22Na+ uptake [22].
• In contrast, this agent does not appreciably inhibit Na+/H+ exchange, measured as 5-(N-ethyl-N-isopropyl)amiloride (EIA)-inhibitable 22Na+ uptake into cultured renal epithelial cells [23].
• In this report, we show that the uptake of octa-arginine (R8) peptide by HeLa cells was significantly suppressed by the macropinocytosis inhibitor ethylisopropylamiloride (EIPA) and the F-actin polymerization inhibitor cytochalasin D, suggesting a role for macropinocytosis in the uptake of the peptide [24].
• Treatment of Black melanocytes with ethyl-isopropyl amiloride (EIPA) caused a rapid dose-dependent inhibition of tyrosinase activity [25].

Associations of Ethylisopropylamiloride with other chemical compounds

• In Na+-free medium, or in presence of the Na+/H+ antiport inhibitors, 5-(N,N-dimethyl)amiloride (DMA) or 5-(N-ethyl-N-isopropyl)amiloride (EIPA), thrombin caused a greater fall of pHi (0.22-0.26 units) that was sustained [26].
• Nigericin (a K+/H+ ionophore) caused a rapid acidification of more than 0.3 pH unit that was sustained in the presence of 5-(N-ethyl-N-isopropyl)amiloride [27].
• In this preparation more than 50% of the rheogenic 22Na+ uptake was blocked by amiloride (IC50 approximately 30 microM), phenamil (IC50 approximately 66 microM), or ethylisopropylamiloride (IC50 approximately 5 microM) [28].
• The ability of ethylisopropylamiloride to prevent nocodazole-induced formation of actin stress fibers in MSV-MDCK cells was more pronounced in Hepes medium relative to NaHCO(3) medium, showing that NHE1 can regulate actin stress fiber assembly in transformed MSV-MDCK cells via its intracellular pH regulatory effect [17].
• Aldosterone 1-10 nmol/l had no effect on channel activity in the presence of 20 micro mol/l ethylisopropylamiloride, an inhibitor of Na(+):H(+) exchange [29].

Gene context of Ethylisopropylamiloride

• Further, exposure of the cells to GM-CSF, IL-3, or TPA results in sustained pHi alkalinizatio, which is abrogated when the cells are preincubated with 5-(N-ethyl-N-isopropyl)amiloride, a specific inhibitor of the antiport [30].
• At a maximum noncytotoxic concentration (25 microM), the potent amiloride analog, 5-(N-ethyl-N-isopropyl)amiloride (EP-Am), decreased but did not abolish, the stimulatory effect of hPRL [31].
• ET-1- but not PMA-stimulated K+ uptake was inhibited by 5-(N-ethyl-N-isopropyl)amiloride (inhibitor of Na+/H+ exchange system), suggesting a linkage of Na+/H+ exchange with ET-1-stimulated Na+,K(+)-ATPase and Na(+)-K(+)-Cl- cotransport activity that is not mediated by PKC [32].
• Cytosolic pH (pHi) was significantly higher in GLUT1 than LacZ cells, an effect abolished in the presence of Na+/H+ exchange inhibitor ethylisopropylamiloride (1 micromol/L) [33].
• When the tubules of the WT mice were exposed to the hyperosmotic solution including either of the two P-gp inhibitors, in the absence of peritubular Na+ or in the presence of peritubular ethylisopropylamiloride (EIPA; the specific inhibitor of Na+/H+ exchange), they did not exhibit RVI [34].

Analytical, diagnostic and therapeutic context of Ethylisopropylamiloride

• Injury was prevented by the Na+-H+ exchange inhibitors ethyl isopropyl amiloride or HOE-694, and the rise of [Ca2+]i at the onset of reperfusion was blocked by HOE-694 [35].
• The protective effects of ischemic preconditioning (IP) and Na+/H+ exchanger blockade (NHEb) by two blockers [ethylisopropylamiloride (EIPA) and HOE 642] were compared in the isovolumic perfused rat heart [36].
• Microinjections of 4,4'-diisothiocyanatostilbene-2,2'-disulphonic acid (DIDS) and acetazolamide (ACZ) induced a marked rise in basal SNA, whereas diethylpyrocarbonate (DEPC) and ethylisopropylamiloride (EIPA) had no significant effect on basal SNA [37].
• In both patient groups ethylisopropylamiloride-sensitive swelling rates were normal compared to the control group indicating a normal activity of the Na+/H+ antiporter [38].
• In LMV, both NHE3 and NHE2 proteins were found by Western blot analysis, but only ethylisopropylamiloride-sensitive and almost completely Hoe-694-resistant Na/H exchange activity was observed from (22)Na uptake and thus attributed to NHE3 [39].

References